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1.
PLoS One ; 15(7): e0235735, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32673328

RESUMO

BACKGROUND: Changes to human body composition reflect changes in health status to some extent. It has been recognized that these changes occur earlier than diseases. This means that a reasonable prediction of body composition helps to improve model users' health. To overcome the low accuracy and poor adaptability of existing human body composition prediction models and obtain higher efficiency, we proposed a novel method for predicting human body composition which uses a modified adaptive genetic algorithm (MAGA). METHODS: Firstly, since there are many parameters for a human body composition model, and these parameters are associated, we designed a new parameter selection approach by combining the improved RReliefF method with the mRMR method. Following this, selected parameters were used to establish a model that fits body composition. Secondly, in order to accurately calculate the weight of parameters in this model, we proposed a solution which used a modified adaptive genetic algorithm, taking advantage of both roulette and optimum reservation strategies. This solution also has an improved selection operator. Thirdly, taking the percentage of body fat (PBF) as an example of body composition, we conducted experiments to compare performance between our algorithm and other algorithms. RESULTS: Through our simulations, we demonstrated that the adaptability of the proposed model is 0.9921, the mean relative error is 0.05%, the mean square error is 1.3 and the correlation coefficient is 0.982. When compared with the indexes of other models, our model has the highest adaptability and the smallest error. Additionally, the suggested model, which has a training time of 28.58s and a running time of 2.84s, is faster than some models. CONCLUSION: The PBF prediction model established by MAGA has high accuracy, stronger generalization ability and higher efficiency, which could provide a new method for human composition prediction.


Assuntos
Algoritmos , Composição Corporal/genética , Corpo Humano , Modelos Genéticos , Seleção Genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
2.
PLoS Med ; 17(7): e1003196, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32692746

RESUMO

BACKGROUND: Melanocortin 4 receptor (MC4R) deficiency, caused by mutations in MC4R, is the most common cause of monogenic forms of obesity. However, these mutations have often been identified in small-scale, case-focused studies. Here, we assess the penetrance of previously reported MC4R mutations at a population level. Furthermore, we examine why some carriers of pathogenic mutations remain of normal weight, to gain insight into the mechanisms that control body weight. METHODS AND FINDINGS: We identified 59 known obesity-increasing mutations in MC4R from the Human Gene Mutation Database (HGMD) and Clinvar. We assessed their penetrance and effect on obesity (body mass index [BMI] ≥ 30 kg/m2) in >450,000 individuals (age 40-69 years) of the UK Biobank, a population-based cohort study. Of these 59 mutations, only 11 had moderate-to-high penetrance and increased the odds of obesity by more than 2-fold. We subsequently focused on these 11 mutations and examined differences between carriers of normal weight and carriers with obesity. Twenty-eight of the 182 carriers of these 11 mutations were of normal weight. Body composition of carriers of normal weight was similar to noncarriers of normal weight, whereas among individuals with obesity, carriers had a somewhat higher BMI than noncarriers (1.44 ± 0.07 standard deviation scores [SDSs] ± standard error [SE] versus 1.29 ± 0.001, P = 0.03), because of greater lean mass (1.44 ± 0.09 versus 1.15 ± 0.002, P = 0.002). Carriers of normal weight more often reported that, already at age 10 years, their body size was below average or average (72%) compared with carriers with obesity (48%) (P = 0.01). To assess the polygenic contribution to body weight in carriers of normal weight and carriers with obesity, we calculated a genome-wide polygenic risk score for BMI (PRSBMI). The PRSBMI of carriers of normal weight (PRSBMI = -0.64 ± 0.18) was significantly lower than of carriers with obesity (0.40 ± 0.11; P = 1.7 × 10-6), and tended to be lower than that of noncarriers of normal weight (-0.29 ± 0.003; P = 0.05). Among carriers, those with a low PRSBMI (bottom quartile) have an approximately 5-kg/m2 lower BMI (approximately 14 kg of body weight for a 1.7-m-tall person) than those with a high PRS (top quartile). Because the UK Biobank population is healthier than the general population in the United Kingdom, penetrance may have been somewhat underestimated. CONCLUSIONS: We showed that large-scale data are needed to validate the impact of mutations observed in small-scale and case-focused studies. Furthermore, we observed that despite the key role of MC4R in obesity, the effects of pathogenic MC4R mutations may be countered, at least in part, by a low polygenic risk potentially representing other innate mechanisms implicated in body weight regulation.


Assuntos
Mutação , Obesidade/genética , Receptor Tipo 4 de Melanocortina/genética , Adulto , Idoso , Bancos de Espécimes Biológicos , Composição Corporal/genética , Índice de Massa Corporal , Peso Corporal/genética , Feminino , Predisposição Genética para Doença , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Penetrância , Reino Unido
3.
Am J Physiol Regul Integr Comp Physiol ; 319(2): R184-R194, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32579386

RESUMO

Recent large genome-wide association studies (GWAS) have independently identified a set of genetic loci associated with lean body mass (LBM) and handgrip strength (HGS). Evaluation of these candidate single-nucleotide polymorphisms (SNPs) may be useful to investigate genetic traits of populations at higher or lower risk of muscle dysfunction. As such, we investigated associations between six SNPs linked to LBM or HGS in a population of elite master athletes (MA) and age-matched controls as a representative population of older individuals with variable maintenance of muscle mass and function. Genomic DNA was isolated from buffy coat samples of 96 individuals [consisting of 48 MA (71 ± 6 yr, age-graded performance 83 ± 9%) and 48 older controls (75 ± 6 yr)]. SNP validation and sample genotyping were conducted using the tetra-primer amplification refractory mutation system (ARMS). For the three SNPs analyzed that were previously associated with LBM (FTO, IRS1, and ADAMTSL3), multinomial logistic regression revealed a significant association of the ADAMTSL3 genotype with %LBM (P < 0.01). For the three HGS-linked SNPs, neither GBF1 nor GLIS1 showed any association with HGS, but for TGFA, multinomial logistic regression revealed a significant association of genotype with HGS (P < 0.05). For ADAMTSL3, there was an enrichment of the effect allele in the MA (P < 0.05, Fisher's exact test). Collectively, of the six SNPs analyzed, ADAMTSL3 and TGFA showed significant associations with LBM and HGS, respectively. The functional relevance of the ADAMTSL3 SNP in body composition and of TGFA in strength may highlight a genetic component of the elite MA phenotype.


Assuntos
Atletas , Composição Corporal/genética , Genótipo , Força da Mão/fisiologia , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Alelos , Índice de Massa Corporal , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo
4.
J Anim Sci ; 98(6)2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32428206

RESUMO

In this study, we aimed to assess the value of genotyping DNA pools as a strategy to generate accurate and cost-effective genomic estimated breeding values (GEBV) of sires in multi-sire mating systems. In order to do that, we used phenotypic records of 2,436 Australian Angus cattle from 174 sires, including yearling weight (YWT; N = 1,589 records), coat score (COAT; N = 2,026 records), and Meat Standards Australia marbling score (MARB; N = 1,304 records). Phenotypes were adjusted for fixed effects and age at measurement and pools of 2, 5, 10, 15, 20, and 25 animals were explored. Pools were created either by phenotype or at random. When pools were created at random, 10 replicates were examined to provide a measure of sampling variation. The relative accuracy of each pooling strategy was measured by the Pearson correlation coefficient between the sire's GEBV with pooled progeny and the GEBV using individually genotyped progeny. Random pools allow the computation of sire GEBV that are, on average, moderately correlated (i.e., r > 0.5 at pool sizes [PS] ≤ 10) with those obtained without pooling. However, for pools assigned at random, the difference between the best and the worst relative accuracy obtained out of the 10 replicates was as high as 0.41 for YWT, 0.36 for COAT, and 0.61 for MARB. This uncertainty associated with the relative accuracy of GEBV makes randomly assigning animals to pools an unreliable approach. In contrast, pooling by phenotype allowed the estimation of sires' GEBV with a relative accuracy ≥ 0.9 at PS < 10 for all three phenotypes. Moreover, even with larger PS, the lowest relative accuracy obtained was 0.88 (YWT, PS = 20). In agreement with results using simulated data, we conclude that pooling by phenotype is a robust approach to implementing genomic evaluation using commercial herd data, and PS larger than 10 individuals can be considered.


Assuntos
Cruzamento , Bovinos/genética , Genoma , Genótipo , Técnicas de Genotipagem/normas , Animais , Austrália , Composição Corporal/genética , Bovinos/classificação , Simulação por Computador , Feminino , Genômica/métodos , Masculino , Reprodutibilidade dos Testes
5.
J Bone Miner Metab ; 38(5): 658-669, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32399675

RESUMO

INTRODUCTION: Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) could affect differentiation of osteoblasts and bone mass through potentiating Wnt/ß-catenin signaling. LGR4 is also relevant to glycolipid metabolism. The present study aims to explore the relationship between genetic variations in LGR4 gene and peak bone mineral density (peak BMD) and body composition phenotypes in Chinese nuclear families. MATERIALS AND METHODS: 22 single-nucleotide polymorphisms (SNPs) were selected and five blocks were constructed in LGR4. Body composition (lean mass and fat mass) and peak BMD were measured by dual-energy X-ray absorptiometry (DXA). Quantitative transmission disequilibrium test (QTDT) analysis was used to explore the relationship between LGR4 genotypes and the mentioned phenotypes. RESULTS: For QTDT analysis after 1000 permutations, significant within-family associations were observed between rs11029986 and total fat mass (TFM) and percentage of TFM (PFM) (P = 0.014 and 0.011, respectively), rs12787344, rs4128868, rs4923445, and rs7936621 and body mass index (BMI) (P = 0.008, 0.003, 0.046, and 0.003, respectively), rs11029986 and total hip BMD (P = 0.026), and rs12796247, rs2219783, and lumbar spine BMD (P = 0.013 and 0.027, respectively). Haplotypes GCGT and AAGC (both in block 3) were observed in significant within-family association with BMI (P = 0.003 and 0.002, respectively). CONCLUSION: It is the first family-based association analysis to explore and demonstrate significant associations between LGR4 genotypes and variations of peak BMD and body composition in young Chinese men. The results are consistent with the findings that recent studies revealed, and confirm the critical relationship between LGR4 gene and both BMD and body composition.


Assuntos
Composição Corporal/genética , Densidade Óssea/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Receptores Acoplados a Proteínas-G/genética , Absorciometria de Fóton , Adiposidade , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Haplótipos/genética , Humanos , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade
6.
Nat Commun ; 11(1): 1841, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32296068

RESUMO

Brain insulin action regulates eating behavior and energy fluxes throughout the body. However, numerous people are brain insulin resistant. How brain insulin responsiveness affects long-term weight and body fat composition in humans is still unknown. Here we show that high brain insulin sensitivity before lifestyle intervention associates with a more pronounced reduction in total and visceral fat during the program. High brain insulin sensitivity is also associated with less regain of fat mass during a nine year follow-up. Cross-sectionally, strong insulin responsiveness of the hypothalamus associates with less visceral fat, while subcutaneous fat is unrelated. Our results demonstrate that high brain insulin sensitivity is linked to weight loss during lifestyle intervention and associates with a favorable body fat distribution. Since visceral fat is strongly linked to diabetes, cardiovascular risk and cancer, these findings have implications beyond metabolic diseases and indicate the necessity of strategies to resolve brain insulin resistance.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Adiposidade/genética , Adiposidade/fisiologia , Adulto , Composição Corporal/genética , Composição Corporal/fisiologia , Encéfalo/metabolismo , Estudos Transversais , Diabetes Mellitus Tipo 2/genética , Feminino , Humanos , Resistência à Insulina/genética , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade
7.
J Dairy Sci ; 103(5): 4510-4516, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32171516

RESUMO

More than 99% of all known Holstein artificial insemination (AI) bulls in the United States can be traced through their male lineage to just 2 bulls born in the 1950s, and all Holstein bulls can be traced back to 2 bulls born in the late 1800s. As the Y chromosome is passed exclusively from sire to son, this suggests that variation is limited for much of the Y chromosome. Two additional male lineages that are separate from modern lineages before 1890 were present at the start of the AI era and had semen available from the USDA National Animal Germplasm Program (Fort Collins, CO). Semen from representatives of those lineages were used for in vitro embryo production by mating to elite modern genetic females, resulting in the birth of 7 bulls and 8 heifers. Genomic evaluation of the bulls suggested that lineages from the beginning of the AI era could be reconstituted to breed average for total economic merit in 1 generation when mated to elite females due to high genetic merit for fertility, near-average genetic merit for fat and protein yield, and below-average genetic merit for udder and physical conformation. Semen from the bulls is commercially available to facilitate Y chromosome research and efforts to restore lost genetic diversity.


Assuntos
Composição Corporal/genética , Bovinos/genética , Indústria de Laticínios , Fertilidade/genética , Variação Genética , Inseminação Artificial/veterinária , Sêmen/fisiologia , Animais , Masculino , Análise do Sêmen/veterinária
8.
J Endocrinol ; 245(1): 165-178, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32053493

RESUMO

Loss of ovarian hormones leads to increased adiposity and insulin resistance (IR), increasing the risk for cardiovascular and metabolic diseases. The purpose of this study was to investigate whether the molecular mechanism behind the adverse systemic and adipose tissue-specific metabolic effects of ovariectomy requires loss of signaling through estrogen receptor alpha (ERα) or estrogen receptor ß (ERß). We examined ovariectomized (OVX) and ovary-intactwild-type (WT), ERα-null (αKO), and ERß-null (ßKO) female mice (age ~49 weeks; n = 7-12/group). All mice were fed a phytoestrogen-free diet (<15 mg/kg) and either remained ovary-intact (INT) or were OVX and followed for 12 weeks. Body composition, energy expenditure, glucose tolerance, and adipose tissue gene and protein expression were analyzed. INT αKO were ~25% fatter with reduced energy expenditure compared to age-matched INT WT controls and ßKO mice (all P < 0.001). Following OVX, αKO mice did not increase adiposity or experience a further increase in IR, unlike WT and ßKO, suggesting that loss of signaling through ERα mediates OVX-induced metabolic dysfunction. In fact, OVX in αKO mice (i.e., signaling through ERß in the absence of ERα) resulted in reduced adiposity, adipocyte size, and IR (P < 0.05 for all). ßKO mice responded adversely to OVX in terms of increased adiposity and development of IR. Together, these findings challenge the paradigm that ERα mediates metabolic protection over ERß in all settings. These findings lead us to suggest that, following ovarian hormone loss, ERß may mediate protective metabolic benefits.


Assuntos
Adiposidade/genética , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Resistência à Insulina/genética , Ovariectomia , Adiponectina/genética , Adiponectina/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Composição Corporal/genética , Metabolismo Energético/genética , Receptor alfa de Estrogênio/deficiência , Receptor beta de Estrogênio/deficiência , Feminino , Expressão Gênica , Humanos , Leptina/genética , Leptina/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais/genética
9.
BMC Med Genet ; 21(1): 40, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093658

RESUMO

BACKGROUND: Sarcopenia is a skeletal muscle disease of clinical importance that occurs commonly in old age and in various disease sub-categories. Widening the scope of knowledge of the genetics of muscle mass and strength is important because it may allow to identify patients with an increased risk to develop a specific musculoskeletal disease or condition such as sarcopenia based on genetic markers. METHODS: We used bioinformatics tools to identify gene loci responsible for regulating muscle strength and lean mass, which can then be a target for downstream lab experimentation validation. Single nuclear polymorphisms (SNPs) associated with various disease traits of muscles and specific genes were chosen according to their muscle phenotype association p-value, as traditionally done in Genome Wide Association Studies, GWAS. We've developed and applied a combination of expression quantitative trait loci (eQTLs) and GWAS summary information, to prioritize causative SNP and point out the unique genes associated in the tissues of interest (muscle). RESULTS: We found NUDT3 and KLF5 for lean mass and HLA-DQB1-AS1 for hand grip strength as candidate genes to target for these phenotypes. The associated regulatory SNPs are rs464553, rs1028883 and rs3129753 respectively. CONCLUSION: Transcriptome Wide Association Studies, TWAS, approaches of combining GWAS and eQTL summary statistics proved helpful in statistically prioritizing genes and their associated SNPs for the disease phenotype of study, in this case, Sarcopenia. Potentially regulatory SNPs associated with these genes, and the genes further prioritized by a scoring system, can be then wet lab verified, depending on the phenotype it is hypothesized to affect.


Assuntos
Hidrolases Anidrido Ácido/genética , Força da Mão , Fatores de Transcrição Kruppel-Like/genética , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Sarcopenia/genética , Magreza/genética , Composição Corporal/genética , Perfilação da Expressão Gênica , Marcadores Genéticos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Cadeias beta de HLA-DQ/genética , Humanos , Desequilíbrio de Ligação , Músculo Esquelético/anatomia & histologia , Músculo Esquelético/metabolismo , Tamanho do Órgão/genética , Fenótipo , Locos de Características Quantitativas , Projetos de Pesquisa , Sarcopenia/complicações , Sarcopenia/epidemiologia , Magreza/complicações , Magreza/epidemiologia
10.
Curr Diab Rep ; 20(1): 1, 2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31970540

RESUMO

PURPOSE OF REVIEW: Our review provides a brief summary of the most recent advances towards the identification of the genetic basis of specific aspects of obesity and the quantification of their consequences on health. We also highlight the most promising avenues to be explored in the future. RECENT FINDINGS: While obesity has been demonstrated to lead to adverse cardio-metabolic consequences, the determinants of inter-individual variability remain largely unknown. The elucidation of the molecular underpinnings of this relationship is hampered by the extremely heterogeneous nature of obesity as a human trait. Recent technological advances have facilitated a more in-depth characterization of body composition at large-scale. At the pace of current data acquisition and resolution, it is realistic to improve characterization of obesity and to advise individuals based on detailed body composition combined with tissue-specific molecular signatures. Individualized predictions of health implications would enable more personalized and effective public health interventions.


Assuntos
Adiposidade/fisiologia , Obesidade/genética , Obesidade/metabolismo , Adiposidade/genética , Composição Corporal/genética , Composição Corporal/fisiologia , Distribuição da Gordura Corporal , Índice de Massa Corporal , Heterogeneidade Genética , Humanos , Obesidade/complicações , Obesidade/diagnóstico , Fenótipo , Fatores Sexuais , Circunferência da Cintura/genética , Circunferência da Cintura/fisiologia
11.
Animal ; 14(6): 1120-1127, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31915094

RESUMO

In order to map quantitative trait loci (QTLs) for allometries of body compositions and metabolic traits in chicken, we phenotypically characterize the allometric growths of multiple body components and metabolic traits relative to BWs using joint allometric scaling models and then establish random regression models (RRMs) to fit genetic effects of markers and minor polygenes derived from the pedigree on the allometric scalings. Prior to statistically inferring the QTLs for the allometric scalings by solving the RRMs, the LASSO technique is adopted to rapidly shrink most of marker genetic effects to zero. Computer simulation analysis confirms the reliability and adaptability of the so-called LASSO-RRM mapping method. In the F2 population constructed by multiple families, we formulate two joint allometric scaling models of body compositions and metabolic traits, in which six of nine body compositions are tested as significant, while six of eight metabolic traits are as significant. For body compositions, a total of 14 QTLs, of which 9 dominant, were detected to be associated with the allometric scalings of drumstick, fat, heart, shank, liver and spleen to BWs; while for metabolic traits, a total of 19 QTLs also including 9 dominant be responsible for the allometries of T4, IGFI, IGFII, GLC, INS, IGR to BWs. The detectable QTLs or highly linked markers can be used to regulate relative growths of the body components and metabolic traits to BWs in marker-assisted breeding of chickens.


Assuntos
Composição Corporal/genética , Galinhas/genética , Locos de Características Quantitativas/genética , Animais , Peso Corporal/genética , Galinhas/fisiologia , Mapeamento Cromossômico/veterinária , Simulação por Computador , Feminino , Ligação Genética , Marcadores Genéticos/genética , Masculino , Fenótipo , Análise de Regressão , Reprodutibilidade dos Testes
12.
Nat Med ; 25(12): 1851-1857, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31792462

RESUMO

Proteins are effector molecules that mediate the functions of genes1,2 and modulate comorbidities3-10, behaviors and drug treatments11. They represent an enormous potential resource for personalized, systemic and data-driven diagnosis, prevention, monitoring and treatment. However, the concept of using plasma proteins for individualized health assessment across many health conditions simultaneously has not been tested. Here, we show that plasma protein expression patterns strongly encode for multiple different health states, future disease risks and lifestyle behaviors. We developed and validated protein-phenotype models for 11 different health indicators: liver fat, kidney filtration, percentage body fat, visceral fat mass, lean body mass, cardiopulmonary fitness, physical activity, alcohol consumption, cigarette smoking, diabetes risk and primary cardiovascular event risk. The analyses were prospectively planned, documented and executed at scale on archived samples and clinical data, with a total of ~85 million protein measurements in 16,894 participants. Our proof-of-concept study demonstrates that protein expression patterns reliably encode for many different health issues, and that large-scale protein scanning12-16 coupled with machine learning is viable for the development and future simultaneous delivery of multiple measures of health. We anticipate that, with further validation and the addition of more protein-phenotype models, this approach could enable a single-source, individualized so-called liquid health check.


Assuntos
Proteínas Sanguíneas/genética , Composição Corporal/genética , Exercício Físico , Medicina de Precisão , Tecido Adiposo/metabolismo , Composição Corporal/fisiologia , Feminino , Humanos , Gordura Intra-Abdominal/metabolismo , Estilo de Vida , Fígado/metabolismo , Masculino , Fatores de Risco
13.
Lipids Health Dis ; 18(1): 212, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31810473

RESUMO

BACKGROUND: Variations in the fat mass and obesity-associated (FTO) gene (16q12.2) are associated with obesity in some populations. This study aimed to determine the relationship between FTO gene polymorphism and adiposity&related markers in Turkish adults was aimed. METHODS: The present study included 200 participants aged 18-65 years, who were genotyped for variants of the FTO gene (rs9939609). Anthropometric measurements were performed. Body compositions were analyzed with Tanita BC 545 N Inner ScanTM. Infrared analyzer (VISCANTM) was also used to determinate the degree of abdominal fat. Body mass index (BMI), body adiposity index (BAI) and lipid accumulation products (LAP) index which are used in body fat estimation were calculated. Body fat amounts were classified using gender-based cut-offs. Odds ratio (OR) and 95% confidence interval (CI) were calculated to determine the risk of having a high body fat amount associated with the risk allele. RESULTS: The frequency of the rs9939609 AA genotype was 19.0%, which was 42.5% for the AT genotype and 38.5% for the TT genotype (wild type). AA genotype was found to be higher in females than in males (26.0 and 12.0%, respectively). The total body fat amount of the individuals with AA genotype was high (28.5 ± 9.25%) compared to AT (27.0 ± 10.31%) and TT (23.7 ± 10.62%) genotype (p < 0.05). However, there was no difference in abdominal fat amounts (%) (AA:38.6%, AT:36.2%, TT:33.7%), internal fat levels and waist/hip ratios (p > 0.05). Significance of association between FTO genotypes and total body fat (%) was retained after adjustment for BMI and gender as well. BMI, LAP, and BAI index values were not different between different genotypes in all individuals and different genders (p > 0.05). CONCLUSION: Our study supports that the FTO rs9939609 polymorphism is associated with fat accumulation in the whole body without being associated with abdominal fat accumulation in Turkish adults.


Assuntos
Gordura Abdominal/metabolismo , Tecido Adiposo/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Predisposição Genética para Doença , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Alelos , Composição Corporal/genética , Índice de Massa Corporal , Feminino , Expressão Gênica , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/metabolismo , Turquia , Circunferência da Cintura , Relação Cintura-Quadril
14.
Nat Commun ; 10(1): 5765, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852892

RESUMO

Body composition is often altered in psychiatric disorders. Using genome-wide common genetic variation data, we calculate sex-specific genetic correlations amongst body fat %, fat mass, fat-free mass, physical activity, glycemic traits and 17 psychiatric traits (up to N = 217,568). Two patterns emerge: (1) anorexia nervosa, schizophrenia, obsessive-compulsive disorder, and education years are negatively genetically correlated with body fat % and fat-free mass, whereas (2) attention-deficit/hyperactivity disorder (ADHD), alcohol dependence, insomnia, and heavy smoking are positively correlated. Anorexia nervosa shows a stronger genetic correlation with body fat % in females, whereas education years is more strongly correlated with fat mass in males. Education years and ADHD show genetic overlap with childhood obesity. Mendelian randomization identifies schizophrenia, anorexia nervosa, and higher education as causal for decreased fat mass, with higher body fat % possibly being a causal risk factor for ADHD and heavy smoking. These results suggest new possibilities for targeted preventive strategies.


Assuntos
Glicemia/genética , Composição Corporal/genética , Transtornos Mentais/genética , Sobrepeso/genética , Fatores Etários , Comorbidade , Escolaridade , Feminino , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Transtornos Mentais/epidemiologia , Transtornos Mentais/prevenção & controle , Pessoa de Meia-Idade , Herança Multifatorial/genética , Sobrepeso/epidemiologia , Fenótipo , Aptidão Física , Fatores de Risco , Fatores Sexuais
15.
Am J Hum Genet ; 105(6): 1222-1236, 2019 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-31761296

RESUMO

Muscle bulk in adult healthy humans is highly variable even after height, age, and sex are accounted for. Low muscle mass, due to fewer and/or smaller constituent muscle fibers, would exacerbate the impact of muscle loss occurring in aging or disease. Genetic variability substantially influences muscle mass differences, but causative genes remain largely unknown. In a genome-wide association study (GWAS) on appendicular lean mass (ALM) in a population of 85,750 middle-aged (aged 38-49 years) individuals from the UK Biobank (UKB), we found 182 loci associated with ALM (p < 5 × 10-8). We replicated associations for 78% of these loci (p < 5 × 10-8) with ALM in a population of 181,862 elderly (aged 60-74 years) individuals from UKB. We also conducted a GWAS on hindlimb skeletal muscle mass of 1,867 mice from an advanced intercross between two inbred strains (LG/J and SM/J); this GWAS identified 23 quantitative trait loci. Thirty-eight positional candidates distributed across five loci overlapped between the two species. In vitro studies of positional candidates confirmed CPNE1 and STC2 as modifiers of myogenesis. Collectively, these findings shed light on the genetics of muscle mass variability in humans and identify targets for the development of interventions for treatment of muscle loss. The overlapping results between humans and the mouse model GWAS point to shared genetic mechanisms across species.


Assuntos
Composição Corporal/genética , Proteínas de Ligação ao Cálcio/genética , Estudo de Associação Genômica Ampla , Glicoproteínas/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Desenvolvimento Muscular/genética , Músculo Esquelético/citologia , Magreza/genética , Adulto , Idoso , Envelhecimento , Animais , Peso Corporal , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Locos de Características Quantitativas
16.
Nat Commun ; 10(1): 5086, 2019 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-31704910

RESUMO

Accurate prediction of an individual's phenotype from their DNA sequence is one of the great promises of genomics and precision medicine. We extend a powerful individual-level data Bayesian multiple regression model (BayesR) to one that utilises summary statistics from genome-wide association studies (GWAS), SBayesR. In simulation and cross-validation using 12 real traits and 1.1 million variants on 350,000 individuals from the UK Biobank, SBayesR improves prediction accuracy relative to commonly used state-of-the-art summary statistics methods at a fraction of the computational resources. Furthermore, using summary statistics for variants from the largest GWAS meta-analysis (n ≈ 700, 000) on height and BMI, we show that on average across traits and two independent data sets that SBayesR improves prediction R2 by 5.2% relative to LDpred and by 26.5% relative to clumping and p value thresholding.


Assuntos
Teorema de Bayes , Herança Multifatorial/genética , Análise de Regressão , Tecido Adiposo , Alopecia/genética , Metabolismo Basal/genética , Bancos de Espécimes Biológicos , Peso ao Nascer/genética , Composição Corporal/genética , Estatura/genética , Índice de Massa Corporal , Densidade Óssea/genética , Diabetes Mellitus Tipo 2/genética , Volume Expiratório Forçado/genética , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único , Estatística como Assunto , Capacidade Vital/genética , Relação Cintura-Quadril
17.
J Dairy Sci ; 102(12): 11609-11621, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31548065

RESUMO

MicroRNA (miRNA) are abundant in milk, and likely have regulatory activity involving lactation and immunity. The objective of this study was to determine the miRNA profile in colostrum of overconditioned cows compared with cows of more moderate body condition score (BCS) at calving. Multiparous cows with either high (≥4.0 on a scale of 1 to 5; n = 7) or moderate BCS (2.75 to 3.50; n = 9) in the week before parturition were selected from a commercial dairy herd. Blood and colostrum were sampled within 24 h after calving. Blood serum was analyzed for free fatty acid (FFA) concentration. MicroRNA was isolated from colostrum samples after removing milk fat and cells. MicroRNA were sequenced, and reads were mapped to the bovine genome and to the existing database of miRNA at miRBase.org. Two programs, Oasis 2.0 and miRDeep2, were employed in parallel for read alignment, and analysis of miRNA count data was performed using DESeq2. Identification of differentially expressed miRNA from DESeq2 was not affected by the differences in miRNA detected by the 2 mapping programs. Most abundant miRNA included miR-30a, miR-148a, miR-181a, let-7f, miR-26a, miR-21, miR-22, and miR-92a. Large-scale shifts in miRNA profile were not observed; however, colostrum of cows with high BCS contained less miR-486, which has been linked with altered glucose metabolism. Colostrum from cows with elevated serum FFA contained less miR-885, which may be connected to hepatic function during the transition period. Potential functions of abundant miRNA suggest involvement in development and maintenance of cellular function in the mammary gland, with the additional possibility of influencing neonatal tissue and immune system development.


Assuntos
Bovinos/fisiologia , Colostro/fisiologia , Ácidos Graxos não Esterificados/sangue , Imunidade/genética , MicroRNAs/análise , Leite/fisiologia , Animais , Animais Recém-Nascidos , Composição Corporal/genética , Bovinos/genética , Bovinos/imunologia , Biologia Computacional , Feminino , Lactação , MicroRNAs/genética , Parto , Gravidez , Interferência de RNA
18.
Growth Factors ; 37(3-4): 153-163, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31500477

RESUMO

The objective of this study was to test the association of the variation in a 360 bp region in exon 2 of the ovine bone morphogenetic protein 4 (BMP4) gene with growth performance (birth weight, pre-weaning average daily gain, weaning weight, post-weaning average daily gain and marketing weight) and body conformational traits (height at withers, height at hips, body length, heart girth, thigh circumference, body mass index, skeletal muscle index, body index and relative body index) in 242 Barki lambs using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP). Two variants (A and B) and three genotypes (AA, AB and BB) were detected. The BMP4 genotype significantly affected (p < .05 or p < .01) post-weaning daily gain, marketing weight, height at hips, thigh circumference, body mass index and skeletal muscle index. The results provided valuable information indicating selection for the BMP4 genotype might increase growth and muscularity in Barki lambs.


Assuntos
Composição Corporal/genética , Tamanho Corporal/genética , Proteína Morfogenética Óssea 4/genética , Ovinos/crescimento & desenvolvimento , Ovinos/genética , Animais , Sequência de Bases , Éxons/genética , Feminino , Variação Genética/genética , Genótipo , Masculino , Fenótipo , Polimorfismo Conformacional de Fita Simples/genética , Análise de Sequência de DNA , Ganho de Peso/genética
19.
PLoS One ; 14(9): e0222141, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31504067

RESUMO

BACKGROUND: Lower birth weight is associated with diabetes although the underlying mechanisms are unclear. Muscle mass could be a modifiable link and hence a target of intervention. We assessed the associations of birth weight with muscle and fat mass observationally in a population with little socio-economic patterning of birth weight and using Mendelian randomization (MR) for validation. METHODS: In the population-representative "Children of 1997" birth cohort (n = 8,327), we used multivariable linear regression to assess the adjusted associations of birth weight (kg) with muscle mass (kg) and body fat (%) at ~17.5 years. Genetically predicted birth weight (effect size) was applied to summary genetic associations with fat-free mass and fat mass (kg) from the UK Biobank (n = ~331,000) to obtain unconfounded estimates using inverse-variance weighting. RESULTS: Observationally, birth weight was positively associated with muscle mass (3.29 kg per kg birth weight, 95% confidence interval (CI) 2.83 to 3.75) and body fat (1.09% per kg birth weight, 95% CI 0.54 to 1.65). Stronger associations with muscle mass were observed in boys than in girls (p for interaction 0.004). Using MR, birth weight was positively associated with fat-free mass (0.77 kg per birth weight z-score, 95% CI 0.22 to 1.33) and fat mass (0.58, 95% CI 0.01 to 1.15). No difference by sex was evident. CONCLUSION: Higher birth weight increasing muscle mass may be relevant to lower birth weight increasing the risk of diabetes and suggests post-natal muscle mass as a potential target of intervention.


Assuntos
Peso ao Nascer/genética , Composição Corporal/genética , China , Feminino , Humanos , Recém-Nascido , Masculino , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único
20.
Am J Physiol Endocrinol Metab ; 317(4): E597-E604, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31386565

RESUMO

It has been suggested that interleukin-6 (IL-6) produced by adipocytes in obesity leads to liver insulin resistance, although this hypothesis has never been definitively tested. Accordingly, we did so by generating adipocyte-specific IL-6-deficient (AdipoIL-6-/-) mice and studying them in the context of diet-induced and genetic obesity. Mice carrying two floxed alleles of IL-6 (C57Bl/6J) were crossed with Cre recombinase-overexpressing mice driven by the adiponectin promoter to generate AdipoIL-6-/- mice. AdipoIL-6-/- and floxed littermate controls were fed a standard chow or high-fat diet (HFD) for 16 wk and comprehensively metabolically phenotyped. In addition to a diet-induced obesity model, we also examined the role of adipocyte-derived IL-6 in a genetic model of obesity and insulin resistance by crossing the AdipoIL-6-/- mice with leptin-deficient (ob/ob) mice. As expected, mice on HFD and ob/ob mice displayed marked weight gain and increased fat mass compared with chow-fed and ob/+ (littermate control) animals, respectively. However, deletion of IL-6 from adipocytes in either model had no effect on glucose tolerance or fasting hyperinsulinemia. We concluded that adipocyte-specific IL-6 does not contribute to whole body glucose intolerance in obese mice.


Assuntos
Adipócitos/metabolismo , Intolerância à Glucose/genética , Interleucina-6/genética , Obesidade/genética , Ganho de Peso/genética , Adiponectina/biossíntese , Adiponectina/genética , Adiposidade/genética , Animais , Composição Corporal/genética , Dieta Hiperlipídica , Intolerância à Glucose/etiologia , Resistência à Insulina/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/complicações , Obesidade/metabolismo
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