Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 554
Filtrar
Más filtros

Banco de datos
Tipo del documento
Intervalo de año de publicación
1.
Hum Mol Genet ; 29(12): 2098-2106, 2020 07 29.
Artículo en Inglés | MEDLINE | ID: mdl-32227112

RESUMEN

Glycosuria is a condition where glucose is detected in urine at higher concentrations than normal (i.e. not detectable). Glycosuria at some point during pregnancy has an estimated prevalence of 50% and is associated with adverse outcomes in both mothers and offspring. Little is currently known about the genetic contribution to this trait or the extent to which it overlaps with other seemingly related traits, e.g. diabetes. We performed a genome-wide association study (GWAS) for self-reported glycosuria in pregnant mothers from the Avon Longitudinal Study of Parents and Children (cases/controls = 1249/5140). We identified two loci, one of which (lead SNP = rs13337037; chromosome 16; odds ratio of glycosuria per effect allele: 1.42; 95% CI: 1.30, 1.56; P = 1.97 × 10-13) was then validated using an obstetric measure of glycosuria measured in the same cohort (227/6639). We performed a secondary GWAS in the 1986 Northern Finland Birth Cohort (NFBC1986; 747/2991) using midwife-reported glycosuria and offspring genotype as a proxy for maternal genotype. The combined results revealed evidence for a consistent effect on glycosuria at the chromosome 16 locus. In follow-up analyses, we saw little evidence of shared genetic underpinnings with the exception of urinary albumin-to-creatinine ratio (Rg = 0.64; SE = 0.22; P = 0.0042), a biomarker of kidney disease. In conclusion, we identified a genetic association with self-reported glycosuria during pregnancy, with the lead SNP located 15kB upstream of SLC5A2, a target of antidiabetic drugs. The lack of strong genetic correlation with seemingly related traits such as type 2 diabetes suggests different genetic risk factors exist for glycosuria during pregnancy.


Asunto(s)
Diabetes Mellitus Tipo 2/genética , Glucosuria/genética , Complicaciones del Embarazo/genética , Transportador 2 de Sodio-Glucosa/genética , Adolescente , Adulto , Índice de Masa Corporal , Cromosomas Humanos Par 16/genética , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/patología , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Genotipo , Glucosuria/epidemiología , Glucosuria/patología , Humanos , Polimorfismo de Nucleótido Simple/genética , Embarazo , Complicaciones del Embarazo/patología , Adulto Joven
2.
Thorax ; 77(2): 164-171, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34155093

RESUMEN

INTRODUCTION: Observational studies suggested lung function is inversely associated with cardiovascular disease (CVD) although these studies could be confounded. We conducted a two sample Mendelian randomisation study using summary statistics from genome-wide association studies (GWAS) to clarify the role of lung function in CVD and its risk factors, and conversely the role of CVD in lung function. METHODS: We obtained genetic instruments for forced expiratory volume in 1 s (FEV1: 260) and forced vital capacity (FVC: 320) from publicly available UK Biobank summary statistics (n=421 986) and applied to GWAS summary statistics for coronary artery disease (CAD) (n=184 305), stroke (n=446 696), atrial fibrillation (n=1 030 836) and heart failure (n=977 320) and cardiovascular risk factors. Inverse variance weighting was used to assess the impact of lung function on these outcomes, with various sensitivity analyses. Bidirectional Mendelian randomisation was used to assess reverse causation. RESULTS: FEV1 and FVC were inversely associated with CAD (OR per SD increase, 0.72 (95% CI 0.63 to 0.82) and 0.70 (95%CI 0.62 to 0.78)), overall stroke (0.87 (95%CI 0.77 to 0.97), 0.90 (95% CI 0.82 to 1.00)) and some stroke subtypes. FEV1 and FVC were inversely associated with type 2 diabetes and systolic blood pressure. Sensitivity analyses produced similar findings although the association with CAD was attenuated after adjusting for height (eg, OR for 1SD FEV10.95 (0.75 to 1.19), but not for stroke or type 2 diabetes. There was no strong evidence for reverse causation. CONCLUSION: Higher lung function likely protect against CAD and stroke.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Estudio de Asociación del Genoma Completo , Humanos , Pulmón , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Factores de Riesgo
3.
PLoS Med ; 17(8): e1003182, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32810184

RESUMEN

BACKGROUND: Fetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. METHODS AND FINDINGS: We performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers' median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02-1.35], P value = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02-1.15], P value = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07-2.23], P value < 0.001), and childhood overweight (OR 1.42 [95% CI 1.35-1.48], P value < 0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52-2.34] instead of OR 2.20 [95% CI 2.02-2.42] when reducing from 5-9 to ≤4 cigarettes/day; OR 2.79 [95% CI 2.39-3.25] and OR 1.93 [95% CI 1.46-2.57] instead of OR 2.95 [95% CI 2.75-3.15] when reducing from ≥10 to 5-9 and ≤4 cigarettes/day, respectively [P values < 0.001]). Reducing the number of cigarettes during pregnancy did not affect the risks of preterm birth and childhood overweight. Among nonsmoking mothers, paternal smoking was associated with childhood overweight (OR 1.21 [95% CI 1.16-1.27], P value < 0.001) but not with adverse birth outcomes. Limitations of this study include the self-report of parental smoking information and the possibility of residual confounding. As this study only included participants from Europe and North America, results need to be carefully interpreted regarding other populations. CONCLUSIONS: We observed that as compared to nonsmoking during pregnancy, quitting smoking in the first trimester is associated with the same risk of preterm birth and small size for gestational age, but with a higher risk of childhood overweight. Reducing the number of cigarettes, without quitting, has limited beneficial effects. Paternal smoking seems to be associated, independently of maternal smoking, with the risk of childhood overweight. Population strategies should focus on parental smoking prevention before or at the start, rather than during, pregnancy.


Asunto(s)
Padres , Obesidad Infantil/epidemiología , Nacimiento Prematuro/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Fumar/efectos adversos , Fumar/epidemiología , Estudios de Cohortes , Europa (Continente)/epidemiología , Femenino , Edad Gestacional , Humanos , Recién Nacido , Masculino , América del Norte/epidemiología , Obesidad Infantil/diagnóstico , Embarazo , Nacimiento Prematuro/diagnóstico , Efectos Tardíos de la Exposición Prenatal/diagnóstico , Factores de Riesgo , Fumar/tendencias
4.
BMC Med ; 18(1): 71, 2020 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-32200763

RESUMEN

BACKGROUND: Age at menarche has been associated with various health outcomes. We aimed to identify potential causal effects of age at menarche on health-related traits in a hypothesis-free manner. METHODS: We conducted a Mendelian randomization phenome-wide association study (MR-pheWAS) of age at menarche with 17,893 health-related traits in UK Biobank (n = 181,318) using PHESANT. The exposure of interest was the genetic risk score for age at menarche. We conducted a second MR-pheWAS after excluding SNPs associated with BMI from the genetic risk score, to examine whether results might be due to the genetic overlap between age at menarche and BMI. We followed up a subset of health-related traits to investigate MR assumptions and seek replication in independent study populations. RESULTS: Of the 17,893 tests performed in our MR-pheWAS, we identified 619 associations with the genetic risk score for age at menarche at a 5% false discovery rate threshold, of which 295 were below a Bonferroni-corrected P value threshold. These included potential effects of younger age at menarche on lower lung function, higher heel bone-mineral density, greater burden of psychosocial/mental health problems, younger age at first birth, higher risk of childhood sexual abuse, poorer cardiometabolic health, and lower physical activity. After exclusion of variants associated with BMI, the genetic risk score for age at menarche was related to 37 traits at a 5% false discovery rate, of which 29 were below a Bonferroni-corrected P value threshold. We attempted to replicate findings for bone-mineral density, lung function, neuroticism, and childhood sexual abuse using 5 independent cohorts/consortia. While estimates for lung function, higher bone-mineral density, neuroticism, and childhood sexual abuse in replication cohorts were consistent with UK Biobank estimates, confidence intervals were wide and often included the null. CONCLUSIONS: The genetic risk score for age at menarche was related to a broad range of health-related traits. Follow-up analyses indicated imprecise evidence of an effect of younger age at menarche on greater bone-mineral density, lower lung function, higher neuroticism score, and greater risk of childhood sexual abuse in the smaller replication samples available; hence, these findings need further exploration when larger independent samples become available.


Asunto(s)
Estudio de Asociación del Genoma Completo/métodos , Menarquia/fisiología , Análisis de la Aleatorización Mendeliana/métodos , Factores de Edad , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad
5.
Clin Endocrinol (Oxf) ; 92(1): 29-37, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31667854

RESUMEN

OBJECTIVE: Bone turnover, which regulates bone mass, may exert metabolic consequences, particularly on markers of glucose metabolism and adiposity. To better understand these relationships, we examined cross-sectional associations between bone turnover markers (BTMs) and metabolic traits in a population with high bone mass (HBM, BMD Z-score ≥+3.2). DESIGN: ß-C-terminal telopeptide of type-I collagen (ß-CTX), procollagen type-1 amino-terminal propeptide (P1NP) and osteocalcin were assessed by electrochemiluminescence immunoassays. Metabolic traits, including lipids and glycolysis-related metabolites, were measured using nuclear magnetic resonance spectroscopy. Associations of BTMs with metabolic traits were assessed using generalized estimating equation linear regression, accounting for within-family correlation, adjusting for potential confounders (age, sex, height, weight, menopause, bisphosphonate and oral glucocorticoid use). RESULTS: A total of 198 adults with HBM had complete data, mean [SD] age 61.6 [13.7] years; 77% were female. Of 23 summary metabolic traits, citrate was positively related to all BTMs: adjusted ßß-CTX  = 0.050 (95% CI 0.024, 0.076), P = 1.71 × 10-4 , ßosteocalcin  = 6.54 × 10-4 (1.87 × 10-4 , 0.001), P = .006 and ßP1NP  = 2.40 × 10-4 (6.49 × 10-5 , 4.14 × 10-4 ), P = .007 (ß = increase in citrate (mmol/L) per 1 µg/L BTM increase). Inverse relationships of ß-CTX (ß = -0.276 [-0.434, -0.118], P = 6.03 × 10-4 ) and osteocalcin (-0.004 [-0.007, -0.001], P = .020) with triglycerides were also identified. We explored the generalizability of these associations in 3664 perimenopausal women (age 47.9 [4.4] years) from a UK family cohort. We confirmed a positive, albeit lower magnitude, association between ß-CTX and citrate (adjusted ßwomen  = 0.020 [0.013, 0.026], P = 1.95 × 10-9 ) and an inverse association of similar magnitude between ß-CTX and triglycerides (ß = -0.354 [-0.471, -0.237], P = 3.03 × 10-9 ). CONCLUSIONS: Bone resorption is positively related to circulating citrate and inversely related to triglycerides. Further studies are justified to determine whether plasma citrate or triglyceride concentrations are altered by factors known to modulate bone resorption, such as bisphosphonates.


Asunto(s)
Densidad Ósea/fisiología , Resorción Ósea/metabolismo , Ácido Cítrico/sangre , Colágeno Tipo I/metabolismo , Osteocalcina/metabolismo , Fragmentos de Péptidos/metabolismo , Péptidos/metabolismo , Perimenopausia/metabolismo , Procolágeno/metabolismo , Triglicéridos/sangre , Adolescente , Adulto , Anciano , Biomarcadores/metabolismo , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Mediciones Luminiscentes , Espectroscopía de Resonancia Magnética , Masculino , Metabolómica , Persona de Mediana Edad , Adulto Joven
6.
Hum Genomics ; 13(1): 6, 2019 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-30704525

RESUMEN

BACKGROUND: Mitochondrial DNA copy number (mtDNA CN) exhibits interindividual and intercellular variation, but few genome-wide association studies (GWAS) of directly assayed mtDNA CN exist. We undertook a GWAS of qPCR-assayed mtDNA CN in the Avon Longitudinal Study of Parents and Children (ALSPAC) and the UK Blood Service (UKBS) cohort. After validating and harmonising data, 5461 ALSPAC mothers (16-43 years at mtDNA CN assay) and 1338 UKBS females (17-69 years) were included in a meta-analysis. Sensitivity analyses restricted to females with white cell-extracted DNA and adjusted for estimated or assayed cell proportions. Associations were also explored in ALSPAC children and UKBS males. RESULTS: A neutrophil-associated locus approached genome-wide significance (rs709591 [MED24], ß (change in SD units of mtDNA CN per allele) [SE] - 0.084 [0.016], p = 1.54e-07) in the main meta-analysis of adult females. This association was concordant in magnitude and direction in UKBS males and ALSPAC neonates. SNPs in and around ABHD8 were associated with mtDNA CN in ALSPAC neonates (rs10424198, ß [SE] 0.262 [0.034], p = 1.40e-14), but not other study groups. In a meta-analysis of unrelated individuals (N = 11,253), we replicated a published association in TFAM (ß [SE] 0.046 [0.017], p = 0.006), with an effect size much smaller than that observed in the replication analysis of a previous in silico GWAS. CONCLUSIONS: In a hypothesis-generating GWAS, we confirm an association between TFAM and mtDNA CN and present putative loci requiring replication in much larger samples. We discuss the limitations of our work, in terms of measurement error and cellular heterogeneity, and highlight the need for larger studies to better understand nuclear genomic control of mtDNA copy number.


Asunto(s)
Variaciones en el Número de Copia de ADN , ADN Mitocondrial/genética , Estudio de Asociación del Genoma Completo/métodos , Adolescente , Adulto , Niño , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple
7.
Eur Heart J ; 40(7): 621-631, 2019 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-30476079

RESUMEN

AIMS: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied. METHODS AND RESULTS: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at 'high' 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29-39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22-24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44-51 such individuals using original algorithms, in contrast to 37-39 individuals with recalibrated algorithms. CONCLUSION: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.


Asunto(s)
Algoritmos , Enfermedades Cardiovasculares/etiología , Anciano , Calibración , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Medición de Riesgo
8.
Diabetologia ; 62(10): 1802-1810, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31451867

RESUMEN

The aetiologies of obesity and type 2 diabetes are incredibly complex, but the potential role of paternal influences remains relatively understudied. A better understanding of paternal influences on offspring risk of obesity and type 2 diabetes could have profound implications for public health, clinical practice and society. In this review, we outline potential biological and social mechanisms through which fathers might exert an impact on the health of their offspring. We also present a systematically compiled overview of the current evidence linking paternal factors to offspring development of obesity and type 2 diabetes throughout the life course. Although evidence is accumulating to support paternal associations with offspring outcomes, more high-quality research is needed to overcome specific methodological challenges and provide stronger causal evidence.


Asunto(s)
Diabetes Mellitus Tipo 2/genética , Obesidad/genética , Animales , Diabetes Mellitus Tipo 2/patología , Epigénesis Genética/genética , Humanos , Obesidad/patología , Herencia Paterna/genética , Herencia Paterna/fisiología
9.
Circulation ; 138(20): 2187-2201, 2018 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-30524135

RESUMEN

Background: Body mass index (BMI) has been suggested to be causally related to cardiovascular health in mid-to-late life, but this has not been explored systematically at younger ages - nor with detailed cardiovascular phenotyping. Recall-by-Genotype (RbG) is an approach that enables the collection of precise phenotypic measures in smaller studies, whilst maintaining statistical power and ability for causal inference. Methods: In this study, we used a combination of conventional multivariable regression analysis, Mendelian randomization (MR) and sub-sample RbG methodologies to estimate the causal effect of BMI on gross-level and detailed cardiovascular health in healthy participants from the Avon Longitudinal Study of Parents and Children at age 17 (N=1420-3108 for different outcomes) and an independent sample from the same cohort (for RbG) study at age 21 (N=386-418). Results: In both MR and RbG analyses, results suggested that higher BMI causes higher blood pressure (BP) and left ventricular mass index (LVMI) in young adults (e.g., difference in LVMI per kg/m2 using MR: 1.07g/m2.7; 95% CI: 0.62, 1.52; P=3.87x10-06 and per 3.58kg/m2 using RbG: 1.65g/m2.7 95% CI: 0.83, 2.47; P=0.0001). Additionally, RbG results suggested a causal role of higher BMI on higher stroke volume (SV: difference per 3.58kg/m2: 1.49ml/m2.04; 95% CI: 0.62, 2.35; P=0.001) and cardiac output (CO: difference per 3.58kg/m2: 0.11l/min/m1.83; 95% CI: 0.03, 0.19; P=0.01) but no strong evidence for a causal role on systemic vascular resistance or total arterial compliance. Neither analysis supported a causal role of higher BMI on heart rate. Conclusions: Complementary MR and RbG causal methodologies, together with a range of sensitivity analyses, suggest that higher BMI is likely to cause worse cardiovascular health, specifically higher BP and LVMI, even in youth. Higher BMI also resulted in increased CO in the RbG study, which appeared to be solely driven by SV, as neither MR nor RbG analyses suggested a causal effect of BMI on heart rate. These consistent results support efforts to reduce BMI from a young age to prevent later adverse cardiovascular health and illustrate the potential for phenotypic resolution with maintained analytical power using RbG.


Asunto(s)
Índice de Masa Corporal , Corazón/fisiología , Análisis de la Aleatorización Mendeliana/métodos , Adiposidad , Adolescente , Grosor Intima-Media Carotídeo , Femenino , Estudio de Asociación del Genoma Completo , Genotipo , Frecuencia Cardíaca , Humanos , Estilo de Vida , Estudios Longitudinales , Masculino , Fenotipo , Polimorfismo de Nucleótido Simple , Análisis de la Onda del Pulso , Resistencia Vascular/fisiología , Función Ventricular Izquierda , Adulto Joven
10.
Circulation ; 138(22): 2499-2512, 2018 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-30524137

RESUMEN

Background: Both statins and PCSK9 inhibitors lower blood low-density lipoprotein cholesterol (LDL-C) levels to reduce risk of cardiovascular events. To assess potential differences between metabolic effects of these two lipid-lowering therapies, we performed detailed lipid and metabolite profiling of a large randomized statin trial and compared the results with the effects of genetic inhibition of PCSK9, acting as a naturally occurring trial. Methods: 228 circulating metabolic measures were quantified by nuclear magnetic resonance spectroscopy, including lipoprotein subclass concentrations and their lipid composition, fatty acids, and amino acids, for 5,359 individuals (2,659 on treatment) in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial at 6-months post-randomization. The corresponding metabolic measures were analyzed in eight population cohorts (N=72,185) using PCSK9 rs11591147 as an unconfounded proxy to mimic the therapeutic effects of PCSK9 inhibitors. Results: Scaled to an equivalent lowering of LDL-C, the effects of genetic inhibition of PCSK9 on 228 metabolic markers were generally consistent with those of statin therapy (R2=0.88). Alterations in lipoprotein lipid composition and fatty acid distribution were similar. However, discrepancies were observed for very-low-density lipoprotein (VLDL) lipid measures. For instance, genetic inhibition of PCSK9 had weaker effects on lowering of VLDL-cholesterol compared with statin therapy (54% vs. 77% reduction, relative to the lowering effect on LDL-C; P=2x10-7 for heterogeneity). Genetic inhibition of PCSK9 showed no significant effects on amino acids, ketones, or a marker of inflammation (GlycA) whereas statin treatment weakly lowered GlycA levels. Conclusions: Genetic inhibition of PCSK9 had similar metabolic effects to statin therapy on detailed lipid and metabolite profiles. However, PCSK9 inhibitors are predicted to have weaker effects on VLDL lipids compared with statins for an equivalent lowering of LDL-C, which potentially translate into smaller reductions in cardiovascular disease risk.


Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Metabolómica/métodos , Proproteína Convertasa 9/metabolismo , Anciano , Anciano de 80 o más Años , Aminoácidos/análisis , Aminoácidos/metabolismo , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/patología , LDL-Colesterol/sangre , VLDL-Colesterol/sangre , Método Doble Ciego , Femenino , Humanos , Masculino , Análisis de la Aleatorización Mendeliana , Inhibidores de PCSK9 , Efecto Placebo , Pravastatina/uso terapéutico , Proproteína Convertasa 9/genética
11.
PLoS Med ; 16(6): e1002828, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31211782

RESUMEN

BACKGROUND: Systematic reviews of randomised controlled trials (RCTs) have suggested that maternal vitamin D (25[OH]D) and calcium supplementation increase birth weight. However, limitations of many trials were highlighted in the reviews. Our aim was to combine genetic and RCT data to estimate causal effects of these two maternal traits on offspring birth weight. METHODS AND FINDINGS: We performed two-sample mendelian randomisation (MR) using genetic instrumental variables associated with 25(OH)D and calcium that had been identified in genome-wide association studies (GWAS; sample 1; N = 122,123 for 25[OH]D and N = 61,275 for calcium). Associations between these maternal genetic variants and offspring birth weight were calculated in the UK Biobank (UKB) (sample 2; N = 190,406). We used data on mother-child pairs from two United Kingdom birth cohorts (combined N = 5,223) in sensitivity analyses to check whether results were influenced by fetal genotype, which is correlated with the maternal genotype (r ≈ 0.5). Further sensitivity analyses to test the reliability of the results included MR-Egger, weighted-median estimator, 'leave-one-out', and multivariable MR analyses. We triangulated MR results with those from RCTs, in which we used randomisation to supplementation with vitamin D (24 RCTs, combined N = 5,276) and calcium (6 RCTs, combined N = 543) as an instrumental variable to determine the effects of 25(OH)D and calcium on birth weight. In the main MR analysis, there was no strong evidence of an effect of maternal 25(OH)D on birth weight (difference in mean birth weight -0.03 g [95% CI -2.48 to 2.42 g, p = 0.981] per 10% higher maternal 25[OH]D). The effect estimate was consistent across our MR sensitivity analyses. Instrumental variable analyses applied to RCTs suggested a weak positive causal effect (5.94 g [95% CI 2.15-9.73, p = 0.002] per 10% higher maternal 25[OH]D), but this result may be exaggerated because of risk of bias in the included RCTs. The main MR analysis for maternal calcium also suggested no strong evidence of an effect on birth weight (-20 g [95% CI -44 to 5 g, p = 0.116] per 1 SD higher maternal calcium level). Some sensitivity analyses suggested that the genetic instrument for calcium was associated with birth weight via exposures that are independent of calcium levels (horizontal pleiotropy). Application of instrumental variable analyses to RCTs suggested that calcium has a substantial effect on birth weight (178 g [95% CI 121-236 g, p = 1.43 × 10-9] per 1 SD higher maternal calcium level) that was not consistent with any of the MR results. However, the RCT instrumental variable estimate may have been exaggerated because of risk of bias in the included RCTs. Other study limitations include the low response rate of UK Biobank, which may bias MR estimates, and the lack of suitable data to test whether the effects of genetic instruments on maternal calcium levels during pregnancy were the same as those outside of pregnancy. CONCLUSIONS: Our results suggest that maternal circulating 25(OH)D does not influence birth weight in otherwise healthy newborns. However, the effect of maternal circulating calcium on birth weight is unclear and requires further exploration with more research including RCT and/or MR analyses with more valid instruments.


Asunto(s)
Peso al Nacer/fisiología , Calcio/sangre , Estudio de Asociación del Genoma Completo/métodos , Análisis de la Aleatorización Mendeliana/métodos , Vitamina D/análogos & derivados , Adulto , Biomarcadores/sangre , Femenino , Variación Genética/genética , Humanos , Recién Nacido , Estudios Longitudinales , Masculino , Salud Materna , Embarazo , Vitamina D/sangre , Vitamina D/genética
12.
Int J Obes (Lond) ; 43(10): 1923-1931, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31332275

RESUMEN

BACKGROUND: Different directions of the association of birthweight with cardio-metabolic health have been found, especially in children, which may be explained by the mediating effect of attained adiposity. We aimed to untangle direct and BMI-mediated associations of birthweight with childhood cardio-metabolic indicators. METHODS: Children from Generation XXI birth cohort were included (n = 4881). Birthweight was abstracted from clinical files. At age 4 and 7, children were re-evaluated. Glucose, triglycerides, LDL-cholesterol, systolic (SBP) and diastolic blood pressure (DBP) z-scores were the cardio-metabolic traits analyzed. Regression coefficients and respective 95% confidence intervals [ß (95%CI)] were computed using path analysis. RESULTS: Birthweight had inverse total effect on SBP at age 4 [-0.005 (-0.010; -0.001)] and 7 [-0.011 (-0.017; -0.006)] and DBP at 7 [-0.008 (-0.012; -0.004)]. Direct effects were found for SBP at 4 [-0.013 (-0.018; -0.009)] and 7 [-0.014 (-0.019; -0.009)], and DBP at 7 [-0.010 (-0.015; -0.006)], explaining the inverse total effects. Positive BMI-mediated indirect effects were found for all cardio-metabolic traits: higher birthweight was associated with higher childhood BMI, which in turn was associated with higher levels of cardio-metabolic traits. CONCLUSIONS: Positive BMI-mediated effect of birthweight on all cardio-metabolic traits was found. However, direct effects were in the opposite direction, significant for blood pressure, which may explain the diversity of results observed in the literature. Combining the direct and BMI-mediated effects, higher birthweight was associated with lower blood pressure at age 7 and have no effect on other cardio-metabolic traits.


Asunto(s)
Peso al Nacer/fisiología , Índice de Masa Corporal , Enfermedades Cardiovasculares/epidemiología , Fenómenos Fisiologicos Nutricionales Maternos/fisiología , Síndrome Metabólico/epidemiología , Obesidad Infantil/epidemiología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Adiposidad , Adulto , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , Niño , Preescolar , Estudios de Cohortes , Dislipidemias/sangre , Dislipidemias/epidemiología , Femenino , Humanos , Hipertensión/sangre , Hipertensión/epidemiología , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/etiología , Encuestas Nutricionales , Obesidad Infantil/sangre , Obesidad Infantil/etiología , Portugal/epidemiología , Embarazo , Efectos Tardíos de la Exposición Prenatal/sangre , Factores de Riesgo
13.
Cancer Causes Control ; 30(1): 63-74, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30506491

RESUMEN

PURPOSE: Breast cancer risk associated with pregnancy characteristics may be mediated by maternal hormones or angiogenic factors. METHODS: We conducted a prospective breast cancer case-control study among women in the Avon Longitudinal Study of Parents and Children (ALSPAC) and Norwegian Mother and Child Cohort Study (MoBa) related to maternal pregnancy prolactin (n = 254 cases and 374 controls), placental growth factor (PlGF, n = 252 and 371), soluble fms-like tyrosine kinase-1 (sFlt-1, n = 118 and 240) and steroid hormone concentrations (ALSPAC only, n = 173 and 171). Odds ratios (OR) and 95% confidence intervals (CI) for a 1 SD change in analytes were estimated using unconditional logistic regression with matching factors (cohort, mother's birth year, serum/plasma, blood collection timing) and gestational age. RESULTS: Breast cancer ORs (95% CI) were 0.85 (0.51-1.43) for estradiol, 0.86 (0.67-1.09) for testosterone, 0.89 (0.71-1.13) for androstenedione, 0.97 (0.71-1.34) for hCG, 0.93 (0.75, 1.15) for prolactin, 1.00 (0.78-1.27) for PlGF and 1.91 (1.00-3.65 ALSPAC) and 0.94 (0.73-1.21 MoBa) for sFlt-1, and were similar adjusting for potential confounders. Results were similar by blood collection timing, parity, age at first birth or diagnosis, and time between pregnancy and diagnosis. CONCLUSION: These data do not provide strong evidence of associations between maternal hormones or angiogenic factors with subsequent maternal breast cancer risk.


Asunto(s)
Proteínas Angiogénicas/metabolismo , Neoplasias de la Mama/patología , Factor de Crecimiento Placentario/metabolismo , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Modelos Logísticos , Estudios Longitudinales , Persona de Mediana Edad , Noruega , Oportunidad Relativa , Embarazo , Estudios Prospectivos
14.
Ann Neurol ; 84(2): 191-199, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-30014513

RESUMEN

OBJECTIVE: Observational studies have shown that increased plasma urate is associated with lower risk of Parkinson's disease (PD), but these studies were not designed to test causality. If a causal relationship exists, then modulating plasma urate levels could be a potential preventive avenue for PD. We used a large two-sample Mendelian randomization (MR) design to assess for a causal relationship between plasma urate and PD risk. METHODS: We used a genetic instrument consisting of 31 independent loci for plasma urate on a case-control genome-wide association study data set, which included 13,708 PD cases and 95,282 controls. Individual effect estimates for each SNP were combined using the inverse-variance weighted (IVW) method. Two additional methods, MR-Egger and a penalized weighted median (PWM)-based approach, were used to assess potential bias attributed to pleiotropy or invalid instruments. RESULTS: We found no evidence for a causal relationship between urate and PD, with an effect estimate from the IVW method of odds ratio (OR) 1.03 (95% confidence interval [CI], 0.88-1.20) per 1-standard-deviation increase in plasma urate levels. MR Egger and PWM analyses yielded similar estimates (OR, 0.99 [95% CI, 0.83-1.17] and 0.99 [95% CI, 0.86-1.14], respectively). INTERPRETATION: We did not find evidence for a linear causal protective effect by urate on PD risk. The associations observed in previous observational studies may be, in part, attributed to confounding or reverse causality. In the context of the present findings, strategies to elevate circulating urate levels may not reduce overall PD risk. Ann Neurol 2018;84:191-199.


Asunto(s)
Variación Genética/genética , Análisis de la Aleatorización Mendeliana/métodos , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple/genética , Ácido Úrico/sangre , Biomarcadores/sangre , Bases de Datos Genéticas/tendencias , Humanos , Enfermedad de Parkinson/diagnóstico
15.
Mov Disord ; 34(12): 1864-1872, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31659794

RESUMEN

BACKGROUND: Mendelian randomization is a method for exploring observational associations to find evidence of causality. OBJECTIVE: To apply Mendelian randomization between risk factors/phenotypic traits (exposures) and PD in a large, unbiased manner, and to create a public resource for research. METHODS: We used two-sample Mendelian randomization in which the summary statistics relating to single-nucleotide polymorphisms from 5,839 genome-wide association studies of exposures were used to assess causal relationships with PD. We selected the highest-quality exposure genome-wide association studies for this report (n = 401). For the disease outcome, summary statistics from the largest published PD genome-wide association studies were used. For each exposure, the causal effect on PD was assessed using the inverse variance weighted method, followed by a range of sensitivity analyses. We used a false discovery rate of 5% from the inverse variance weighted analysis to prioritize exposures of interest. RESULTS: We observed evidence for causal associations between 12 exposures and risk of PD. Of these, nine were effects related to increasing adiposity and decreasing risk of PD. The remaining top three exposures that affected PD risk were tea drinking, time spent watching television, and forced vital capacity, but these may have been biased and were less convincing. Other exposures at nominal statistical significance included inverse effects of smoking and alcohol. CONCLUSIONS: We present a new platform which offers Mendelian randomization analyses for a total of 5,839 genome-wide association studies versus the largest PD genome-wide association studies available (https://pdgenetics.shinyapps.io/MRportal/). Alongside, we report further evidence to support a causal role for adiposity on lowering the risk of PD. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.


Asunto(s)
Análisis de la Aleatorización Mendeliana/métodos , Enfermedad de Parkinson/genética , Adulto , Anciano , Anciano de 80 o más Años , Causalidad , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo , , Televisión , Resultado del Tratamiento , Capacidad Vital
16.
JAMA ; 321(17): 1702-1715, 2019 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-31063572

RESUMEN

Importance: Both low and high gestational weight gain have been associated with adverse maternal and infant outcomes, but optimal gestational weight gain remains uncertain and not well defined for all prepregnancy weight ranges. Objectives: To examine the association of ranges of gestational weight gain with risk of adverse maternal and infant outcomes and estimate optimal gestational weight gain ranges across prepregnancy body mass index categories. Design, Setting, and Participants: Individual participant-level meta-analysis using data from 196 670 participants within 25 cohort studies from Europe and North America (main study sample). Optimal gestational weight gain ranges were estimated for each prepregnancy body mass index (BMI) category by selecting the range of gestational weight gain that was associated with lower risk for any adverse outcome. Individual participant-level data from 3505 participants within 4 separate hospital-based cohorts were used as a validation sample. Data were collected between 1989 and 2015. The final date of follow-up was December 2015. Exposures: Gestational weight gain. Main Outcomes and Measures: The main outcome termed any adverse outcome was defined as the presence of 1 or more of the following outcomes: preeclampsia, gestational hypertension, gestational diabetes, cesarean delivery, preterm birth, and small or large size for gestational age at birth. Results: Of the 196 670 women (median age, 30.0 years [quartile 1 and 3, 27.0 and 33.0 years] and 40 937 were white) included in the main sample, 7809 (4.0%) were categorized at baseline as underweight (BMI <18.5); 133 788 (68.0%), normal weight (BMI, 18.5-24.9); 38 828 (19.7%), overweight (BMI, 25.0-29.9); 11 992 (6.1%), obesity grade 1 (BMI, 30.0-34.9); 3284 (1.7%), obesity grade 2 (BMI, 35.0-39.9); and 969 (0.5%), obesity grade 3 (BMI, ≥40.0). Overall, any adverse outcome occurred in 37.2% (n = 73 161) of women, ranging from 34.7% (2706 of 7809) among women categorized as underweight to 61.1% (592 of 969) among women categorized as obesity grade 3. Optimal gestational weight gain ranges were 14.0 kg to less than 16.0 kg for women categorized as underweight; 10.0 kg to less than 18.0 kg for normal weight; 2.0 kg to less than 16.0 kg for overweight; 2.0 kg to less than 6.0 kg for obesity grade 1; weight loss or gain of 0 kg to less than 4.0 kg for obesity grade 2; and weight gain of 0 kg to less than 6.0 kg for obesity grade 3. These gestational weight gain ranges were associated with low to moderate discrimination between those with and those without adverse outcomes (range for area under the receiver operating characteristic curve, 0.55-0.76). Results for discriminative performance in the validation sample were similar to the corresponding results in the main study sample (range for area under the receiver operating characteristic curve, 0.51-0.79). Conclusions and Relevance: In this meta-analysis of pooled individual participant data from 25 cohort studies, the risk for adverse maternal and infant outcomes varied by gestational weight gain and across the range of prepregnancy weights. The estimates of optimal gestational weight gain may inform prenatal counseling; however, the optimal gestational weight gain ranges had limited predictive value for the outcomes assessed.


Asunto(s)
Índice de Masa Corporal , Ganancia de Peso Gestacional , Complicaciones del Embarazo , Resultado del Embarazo , Adulto , Peso al Nacer , Cesárea/estadística & datos numéricos , Diabetes Gestacional , Femenino , Humanos , Hipertensión Inducida en el Embarazo , Recién Nacido , Obesidad , Embarazo , Nacimiento Prematuro
17.
Diabetologia ; 61(1): 242-252, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29064033

RESUMEN

AIMS/HYPOTHESIS: There is evidence that, from birth, South Asians are fatter, for a given body mass, than Europeans. The role of developmental overnutrition related to maternal adiposity and circulating glucose in these ethnic differences is unclear. Our aim was to compare associations of maternal gestational adiposity and glucose with adiposity at age 4/5 years in white British and Pakistani children. METHODS: Born in Bradford is a prospective study of children born between 2007 and 2010 in Bradford, UK. Mothers completed an OGTT at 27-28 weeks of gestation. We examined associations between maternal gestational BMI, fasting glucose, post-load glucose and diabetes (GDM) and offspring height, weight, BMI and subscapular skinfold (SSF) and triceps skinfold (TSF) thickness at age 4/5 years, using data from 6060 mother-offspring pairs (2717 [44.8%] white British and 3343 [55.2%] Pakistani). RESULTS: Pakistani mothers had lower BMI and higher fasting and post-load glucose and were twice as likely to have GDM (defined using modified WHO criteria) than white British women (15.8% vs 6.9%). Pakistani children were taller and had lower BMI than white British children; they had similar SSF and lower TSF. Maternal BMI was positively associated with the adiposity of offspring in both ethnic groups, with some evidence of stronger associations in Pakistani mother-offspring pairs. For example, the difference in adjusted mean BMI per 1 kg/m2 greater maternal BMI was 0.07 kg/m2 (95% CI 0.05, 0.08) and 0.10 kg/m2 (95% CI 0.09. 0.11) in white British and Pakistani children, respectively, with equivalent results for SSF being 0.07 mm (95% CI 0.05, 0.08) and 0.09 mm (95% CI 0.08. 0.11) (p for ethnic difference < 0.03 for both). There was no strong evidence of association of fasting and post-load glucose, or GDM, with outcomes in either group. CONCLUSIONS/INTERPRETATION: At age 4/5 years, Pakistani children are taller and lighter than white British children. While maternal BMI is positively associated with offspring adiposity, gestational glycaemia is not clearly related to offspring adiposity in either ethnic group.


Asunto(s)
Adiposidad/fisiología , Exposición Materna/efectos adversos , Pueblo Asiatico , Glucemia/metabolismo , Índice de Masa Corporal , Preescolar , Femenino , Humanos , Masculino , Obesidad/metabolismo , Pakistán , Embarazo , Estudios Prospectivos , Reino Unido , Población Blanca
18.
Circulation ; 135(24): 2373-2388, 2017 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-28500271

RESUMEN

BACKGROUND: The implications of different adiposity measures on cardiovascular disease etiology remain unclear. In this article, we quantify and contrast causal associations of central adiposity (waist-to-hip ratio adjusted for body mass index [WHRadjBMI]) and general adiposity (body mass index [BMI]) with cardiometabolic disease. METHODS: Ninety-seven independent single-nucleotide polymorphisms for BMI and 49 single-nucleotide polymorphisms for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with coronary heart disease (CHD) data from CARDIoGRAMplusC4D (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics; combined total 66 842 cases), stroke from METASTROKE (12 389 ischemic stroke cases), type 2 diabetes mellitus from DIAGRAM (Diabetes Genetics Replication and Meta-analysis; 34 840 cases), and lipids from GLGC (Global Lipids Genetic Consortium; 213 500 participants) consortia. Primary outcomes were CHD, type 2 diabetes mellitus, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits. RESULTS: Each one standard deviation (SD) higher WHRadjBMI (1 SD≈0.08 U) associated with a 48% excess risk of CHD (odds ratio [OR] for CHD, 1.48; 95% confidence interval [CI], 1.28-1.71), similar to findings for BMI (1 SD≈4.6 kg/m2; OR for CHD, 1.36; 95% CI, 1.22-1.52). Only WHRadjBMI increased risk of ischemic stroke (OR, 1.32; 95% CI, 1.03-1.70). For type 2 diabetes mellitus, both measures had large effects: OR, 1.82 (95% CI, 1.38-2.42) and OR, 1.98 (95% CI, 1.41-2.78) per 1 SD higher WHRadjBMI and BMI, respectively. Both WHRadjBMI and BMI were associated with higher left ventricular hypertrophy, glycemic traits, interleukin 6, and circulating lipids. WHRadjBMI was also associated with higher carotid intima-media thickness (39%; 95% CI, 9%-77% per 1 SD). CONCLUSIONS: Both general and central adiposity have causal effects on CHD and type 2 diabetes mellitus. Central adiposity may have a stronger effect on stroke risk. Future estimates of the burden of adiposity on health should include measures of central and general adiposity.


Asunto(s)
Adiposidad/genética , Distribución de la Grasa Corporal/métodos , Enfermedad Coronaria/genética , Diabetes Mellitus Tipo 2/genética , Análisis de la Aleatorización Mendeliana/métodos , Accidente Cerebrovascular/genética , Enfermedad Coronaria/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Humanos , Estudios Longitudinales , Estudios Observacionales como Asunto/métodos , Polimorfismo de Nucleótido Simple/genética , Estudios Prospectivos , Accidente Cerebrovascular/epidemiología
19.
Am J Epidemiol ; 187(4): 677-686, 2018 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-29020129

RESUMEN

Earlier puberty and menarche are associated with adverse health outcomes. Reported associations of maternal adiposity with daughter's age at menarche are inconsistent. We examined associations between maternal prepregnancy body mass index (BMI; weight (kg)/height (m)2) and gestational weight gain (GWG) and daughter's ages at menarche (n = 3,935 mother-offspring pairs), pubarche (Tanner stage 2 for pubic hair) (n = 2,942 pairs), and thelarche (Tanner stage 2 for breast development) (n = 2,942 pairs) in the Avon Longitudinal Study of Parents and Children, a prospective United Kingdom pregnancy cohort study (baseline 1991-1992). During a follow-up period of up to 17 years (1991-2008), mean menarcheal age was 12.6 (standard deviation, 1.2) years. Both maternal prepregnancy BMI and GWG were inversely associated with daughter's age at menarche after adjustment for maternal age, parity, socioeconomic status, smoking, maternal menarcheal age, and ethnicity (mean differences were -0.34 months (95% confidence interval: -0.45, -0.22) per BMI unit and -0.17 months (95% confidence interval: -0.26, -0.07) per kg, respectively). Associations remained unchanged after adjustment for birth weight and gestational age but were attenuated to the null when results were adjusted for daughter's prepubertal BMI. Similar results were found for ages at pubarche and thelarche. These findings indicate that greater prepregnancy BMI and GWG are associated with earlier puberty in daughters and that these associations are mediated by daughters' prepubertal BMIs.


Asunto(s)
Índice de Masa Corporal , Ganancia de Peso Gestacional , Menarquia , Núcleo Familiar , Sobrepeso/epidemiología , Adolescente , Adulto , Factores de Edad , Peso al Nacer , Niño , Femenino , Edad Gestacional , Humanos , Estudios Longitudinales , Edad Materna , Estudios Prospectivos , Reino Unido
20.
Hum Mol Genet ; 25(2): 382-8, 2016 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-26604150

RESUMEN

Anti-Müllerian hormone (AMH) is an essential messenger of sexual differentiation in the foetus and is an emerging biomarker of postnatal reproductive function in females. Due to a paucity of adequately sized studies, the genetic determinants of circulating AMH levels are poorly characterized. In samples from 2815 adolescents aged 15 from the ALSPAC study, we performed the first genome-wide association study of serum AMH levels across a set of ∼9 m '1000 Genomes Reference Panel' imputed genetic variants. Genetic variants at the AMH protein-coding gene showed considerable allelic heterogeneity, with both common variants [rs4807216 (P(Male) = 2 × 10(-49), Beta: ∼0.9 SDs per allele), rs8112524 (P(Male) = 3 × 10(-8), Beta: ∼0.25)] and low-frequency variants [rs2385821 (P(Male) = 6 × 10(-31), Beta: ∼1.2, frequency 3.6%)] independently associated with apparently large effect sizes in males, but not females. For all three SNPs, we highlight mechanistic links to AMH gene function and demonstrate highly significant sex interactions (P(Het) 0.0003-6.3 × 10(-12)), culminating in contrasting estimates of trait variance explained (24.5% in males versus 0.8% in females). Using these SNPs as a genetic proxy for AMH levels, we found no evidence in additional datasets to support a biological role for AMH in complex traits and diseases in men.


Asunto(s)
Hormona Antimülleriana/genética , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Adolescente , Alelos , Hormona Antimülleriana/sangre , Femenino , Genes , Humanos , Masculino , Factores Sexuales
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA