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1.
Hum Mol Genet ; 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31504550

RESUMO

Although hundreds of GWAS-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity, and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of thirty studies consisting of up to 13,005 cases (≥95th percentile of BMI achieved 2-18 years old) and 15,599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1,888 cases and 4,689 controls from seven cohorts of European and North/South American ancestry. In addition to observing eighteen previously implicated BMI or obesity loci, for both early and late onset, we uncovered one completely novel locus in this trans-ancestral analysis (nearest gene: METTL15). The variant was nominally associated in only the European subgroup analysis but had a consistent direction of effect in other ethnicities. We then utilized trans-ancestral Bayesian analysis to narrow down the location of the probable causal variant at each genome-wide significant signal. Of all the fine-mapped loci, we were able to narrow down the causative variant at four known loci to fewer than ten SNPs (FAIM2, GNPDA2, MC4R and SEC16B loci). In conclusion, an ethnically diverse setting has enabled us to both identify an additional pediatric obesity locus and further fine-map existing loci.

3.
Eur J Obstet Gynecol Reprod Biol ; 238: 44-48, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31082743

RESUMO

OBJECTIVE: To test whether maternal hemoglobin during pregnancy associates with offspring perinatal outcomes in a developed country. Changes in maternal hemoglobin concentration during pregnancy are partly physiological phenomena reflecting alterations of maternal blood volume. Especially hemoglobin measures outside the physiological range may influence maternal health and fetal growth with long-lasting consequences. STUDY DESIGN: We studied an unselected sample drawn from two regional birth cohorts born 20 years apart: The Northern Finland Birth Cohorts 1966 and 1986. These are two mother-and-child population-based birth cohorts together comprising 21,710 mothers and their children. After exclusions, the sample size of the current study was 20,554. Concentrations of maternal hemoglobin at first and last antenatal visits were categorized as low (lowest 10%), medium (reference) or high (highest 10%). Multinomial logistic regression analyses for categories of maternal hemoglobin and perinatal outcomes such as preterm delivery and full-term small and large for gestational age were conducted with adjustments for maternal cofactors. RESULTS: Low maternal hemoglobin at early pregnancy associated with decreased risk of full-term small for gestational age (adjusted OR 0.73, 95% CI [0.58, 0.93], p = 0.010). At late pregnancy, low maternal hemoglobin associated with increased risk of preterm delivery (adjusted OR 1.60, 95% CI [1.26, 2.02], p < 0.0005) whereas high maternal hemoglobin associated with increased risk of full-term small for gestational age (adjusted OR 1.29, 95% CI [1.07, 1.56], p = 0.009). Maternal hemoglobin did not show constant association with risk of large for gestational age. CONCLUSION: The results from this study support evidence that both low and high maternal hemoglobin associate with adverse perinatal outcomes. Low maternal hemoglobin associated with preterm delivery and high with full-term small for gestational age. Association was mainly present when maternal hemoglobin was measured during the third trimester. These results indicate that it is important to monitor both extremes of maternal hemoglobin throughout the pregnancy.

4.
EBioMedicine ; 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30442561

RESUMO

BACKGROUND: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health. METHODS: We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n = 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), diastolic, and systolic blood pressure (BP). FINDINGS: Lower DNA methylation at three out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Lower DNA methylation at cg14179389, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P < 0·012. In contrast, lower DNA methylation at cg09935388, the strongest adult own smoking locus, was associated with decreased BMI, WC, and BP (adjusted 1 × 10-7 < P < 0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 × 10-8 < P < 0.001). Lower DNA methylation at all the CpGs was consistently associated with higher TG levels. INTERPRETATION: Epigenetic changes at the GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors. FUND: European Union's Horizon 2020 research and innovation programme under grant agreement no. 633595 DynaHEALTH.

5.
Int J Obes (Lond) ; 2018 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-30120425

RESUMO

BACKGROUND: The prevention of the risk of type 2 diabetes (T2D) is complicated by multidimensional interplays between biological and psychosocial factors acting at the individual level. To address the challenge we took a systematic approach, to explore the bio-psychosocial predictors of blood glucose in mid-age. METHODS: Based on the 31-year and 46-year follow-ups (5,078 participants, 43% male) of Northern Finland Birth Cohort 1966, we used a systematic strategy to select bio-psychosocial variables at 31 years to enable a data-driven approach. As selection criteria, the variable must be (i) a component of the metabolic syndrome or an indicator of psychosocial health using WHO guidelines, (ii) easily obtainable in general health check-ups and (iii) associated with fasting blood glucose at 46 years (P < 0.10). Exploratory and confirmatory factor analysis were used to derive latent factors, and stepwise linear regression allowed exploration of relationships between factors and fasting glucose. RESULTS: Of all 26 variables originally considered, 19 met the selection criteria and were included in an exploratory factor analysis. Two variables were further excluded due to low loading (<0.3). We derived four latent factors, which we named as socioeconomic, metabolic, psychosocial and blood pressure status. The combination of metabolic and psychosocial factors, adjusted for sex, provided best prediction of fasting glucose at 46 years (explaining 10.7% of variation in glucose; P < 0.001). Regarding different bio-psychosocial pathways and relationships, the importance of psychosocial factors in addition to established metabolic risk factors was highlighted. CONCLUSIONS: The present study supports evidence for the bio-psychosocial nature of adult glycemic health and exemplifies an evidence-based approach to model the bio-psychosocial relationships. The factorial model may help further research and public health practice in focusing also on psychosocial aspects in maintaining normoglycaemia in the prevention of cardio-metabolic diseases.

6.
Schizophr Bull ; 44(5): 1151-1158, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-29237066

RESUMO

Delayed motor developmental milestones have been reported to be associated with schizophrenia in previous studies, but no study has examined the relationship between early motor developmental milestones and schizotypy. We have examined this relationship in a prospective birth cohort.In the Northern Finland Birth Cohort 1966, data on 9 early motor developmental milestones were collected prospectively from visits to child welfare centers, and data on adult schizotypy were collected through a questionnaire (N = 4557-4674). Positive schizotypy was measured by the Perceptual Aberration Scale (PAS), negative schizotypy was measured by Physical Anhedonia Scale (PhAS) and Social Anhedonia Scale (SAS). Three related scales were included: Schizoidia Scale (SCHD), Hypomanic Personality Scale (HPS), and Bipolar II Scale (BIP2). We examined the milestone-schizotypy associations before and after excluding cases of schizophrenia from this population-based sample. Hierarchical regression analyses adjusted for covariates and separately for both genders were performed. In men, each extra month of delay in achievement of touching thumb with index finger, sitting unsupported, standing up, walking with support, or walking unsupported was associated with an increase in PAS, PhAS, or SCHD scores, or decrease in BIP2 score (P < .05). In women, each extra month of delay in achievement of turning from back to tummy was associated with an increase in PhAS and SAS scores (P < .05). Schizotypy is associated with delayed motor developmental milestones in early-life, but there is some heterogeneity with regards to types of milestones and gender. These findings suggest delayed motor development confers risk across the continuum of schizophrenia syndrome.

7.
BMJ Open ; 7(3): e013161, 2017 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-28264828

RESUMO

OBJECTIVE: Evidence from randomised controlled trials suggests that vitamin D may reduce multimorbidity, but very few studies have investigated specific determinants of vitamin D2 and D3 (two isoforms of 25-hydroxyvitamin D). The aim of the study was to investigate the determinants of vitamin D2 and D3 and to identify the risk factors associated with hypovitaminosis D. DESIGN: Cross-sectional study. SETTING: Northern Finland Birth Cohort 1966. PARTICIPANTS: 2374 male and 2384 female participants with data on serum 25(OH)D2 and 25(OH)D3 concentrations measured at 31 years of age (1997), together with comprehensive measures of daylight, anthropometric, social, lifestyle and contraceptive cofactors. METHODS: We assessed a wide range of potential determinants prior to a nationwide fortification programme introduced in Finland. The determinants of 25(OH)D2, 25(OH)D3 and 25(OH)D concentrations were analysed by linear regression and risk factors for being in lower tertile of 25(OH)D concentration by ordinal logistic regression. RESULTS: At the time of sampling, 72% of the participants were vitamin D sufficient (≥50 nmol/L). Low sunlight exposure period (vs high) was associated positively with 25(OH)D2 and negatively with 25(OH)D3 concentrations. Use of oral contraceptives (vs non-users) was associated with an increase of 0.17 nmol/L (95% CI 0.08 to 0.27) and 0.48 nmol/L (95% CI 0.41 to 0.56) in 25(OH)D2 and 25(OH)D3 concentrations. Sex, season, latitude, alcohol consumption and physical activity were the factors most strongly associated with 25(OH)D concentration. Risk factors for low vitamin D status were low sunlight exposure defined by time of sampling, residing in northern latitudes, obesity, higher waist circumference, low physical activity and unhealthy diet. CONCLUSIONS: We demonstrate some differential associations of environmental and lifestyle factors with 25(OH)D2 and 25(OH)D3 raising important questions related to personalised healthcare. Future strategies could implement lifestyle modification and supplementation to improve vitamin D2 and D3 status, accounting for seasonal, lifestyle, metabolic and endocrine status.


Assuntos
Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Vitamina D/sangue , Adulto , Antropometria , Anticoncepção , Estudos Transversais , Feminino , Finlândia/epidemiologia , Humanos , Estilo de Vida , Masculino , Fatores de Risco , Luz Solar , Vitamina D/análogos & derivados
8.
J Clin Pharmacol ; 52(10): 1584-91, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22167569

RESUMO

The Drug Burden Index (DBI) is associated with poorer physical function in stable, community-dwelling, older people. The authors speculated that a higher DBI is associated with reduced physical function (Barthel Index, primary outcome) and predicts adverse outcomes (length of stay, in-hospital mortality, secondary outcomes) in frail, acutely ill, older hospitalized patients. Clinical and demographic characteristics, Barthel Index, DBI, and full medication exposure were recorded on admission in 362 consecutive patients (84 ± 7 years old) admitted to 2 acute geriatric units between February 1, 2010, and June 30, 2010. A unit increase in DBI was associated with a 29% reduction in the odds of being in a higher Barthel Index quartile than a lower quartile (odds ratio, 0.71; 95% confidence interval, 0.55-0.91; P = .007). The Barthel Index components mostly affected were bathing (P < .001), grooming (P < .001), dressing (P = .001), bladder function (P < .001), transfers (P = .001), mobility (P < .001), and stairs (P < .001). A higher DBI independently predicted length of stay (hazard ratio, 1.23; 95% confidence interval, 1.06-1.42; P = .005) but not in-hospital mortality (hazard ratio, 1.17; 95% confidence interval, 0.72-1.90; P = .52). Higher DBI scores on admission are independently associated with lower scores of the Barthel Index and predict length of stay among older hospitalized patients. The DBI may be useful in the acute setting to improve risk stratification.


Assuntos
Atividades Cotidianas , Uso de Medicamentos/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Antagonistas Colinérgicos/administração & dosagem , Feminino , Mortalidade Hospitalar , Humanos , Hipnóticos e Sedativos/administração & dosagem , Masculino , Polimedicação
9.
J Am Med Dir Assoc ; 12(8): 565-572, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21514242

RESUMO

OBJECTIVES: The anticholinergic risk scale (ARS) score is associated with the number of anticholinergic side effects in older outpatients. We tested the hypothesis that high ARS scores are negatively associated with "global" parameters of physical function (Barthel Index, primary outcome) and predict length of stay and in-hospital mortality (secondary outcomes) in older hospitalized patients. DESIGN AND SETTING: Prospective study in 2 acute geriatric units. PARTICIPANTS: Three hundred sixty-two consecutive patients (age 83.6 ± 6.6 years) admitted between February 1, 2010, and June 30, 2010. MEASUREMENTS: Clinical and demographic characteristics, Barthel Index, full medication exposure, and ARS score were recorded on admission. Data on length of stay and in-hospital mortality were obtained from electronic records. RESULTS: After adjustment for age, gender, dementia, institutionalization, Charlson Comorbidity Index, admission site, and number of nonanticholinergic drugs, a unit increase in ARS score was associated with a 29% reduction in the odds of being in a higher Barthel quartile than a lower quartile (odds ratio 0.71, 95% confidence interval [CI] 0.59-0.86, P = .001). The Barthel components mostly affected were bathing (P < .001), grooming (P < .001), dressing (P < .001), transfers (P =.005), mobility (P < .001), and stairs (P < .001). Higher ARS scores predicted in-hospital mortality among patients with hyponatremia (hazard ratio [HR] 3.66, 95% CI 1.70-7.89, P = .001) but not those without hyponatremia (HR 1.04, 95% CI 0.70-1.54, P = .86). The ARS score did not significantly predict length of stay (HR 1.02, 95% CI 0.88-1.17, P = .82). CONCLUSION: High ARS scores are negatively associated with various components of the Barthel Index and predict in-hospital mortality in the presence of hyponatremia among older patients. The ARS score may be useful in the acute setting to improve risk stratification.


Assuntos
Antagonistas Colinérgicos/efeitos adversos , Hospitalização , Limitação da Mobilidade , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Enfermagem Geriátrica , Mortalidade Hospitalar , Humanos , Tempo de Internação , Avaliação de Resultados (Cuidados de Saúde) , Estudos Prospectivos , Medição de Risco , Escócia
10.
Hosp Pract (1995) ; 39(1): 30-6, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21441756

RESUMO

BACKGROUND: Antimuscarinic drug prescribing scoring systems might better identify patients at risk of adverse drug reactions. The recently developed Anticholinergic Risk Scale (ARS) score is significantly associated with the number of antimuscarinic side effects in older outpatients. We sought to identify the clinical and demographic patient-level correlates of the ARS, including a modified version adjusted for daily dose, in elderly hospitalized patients. METHODS: Clinical and demographic patient characteristics known to be associated with antimuscarinic prescribing, ARS and dose-adjusted ARS scores, and full medication exposure on admission were recorded in 362 consecutive patients (aged 83.6 ± 6.6 years) admitted to 2 geriatric units (NHS Grampian, Aberdeen, Scotland, UK) between February 1, 2010 and June 30, 2010. RESULTS: Each year of increasing age was associated with reduced number of antimuscarinic drugs (incidence rate ratio [IRR], 0.963; 95% confidence interval [CI], 0.948-0.980; P < 0.001), non-antimuscarinic drugs (IRR, 0.991; 95% CI, 0.985-0.997; P = 0.006), and total number of drugs (IRR, 0.988; 95% CI, 0.983-0.994; P < 0.001). Multivariate Poisson regression showed that increasing age and history of dementia were negatively associated with the ARS score (IRR, 0.97; 95% CI, 0.94-0.99; P = 0.001 and IRR, 0.62; 95% CI, 0.41-0.92; P = 0.019, respectively). By contrast, institutionalization (IRR, 1.32; 95% CI, 1.00-1.74; P = 0.050), Charlson comorbidity index (IRR, 1.06; 95% CI, 1.01-1.11; P = 0.015), and total number of non-antimuscarinic drugs (IRR, 1.13; 95% CI, 1.08-1.18; P < 0.001) were all positively associated with the ARS score. Similar results were observed for the dose-adjusted ARS score. CONCLUSION: Institutionalization, comorbidities, and non-antimuscarinic polypharmacy show independent positive associations with the ARS and dose-adjusted ARS scores in older hospitalized patients. Increasing age and dementia are negatively associated with the ARS score.


Assuntos
Antagonistas Muscarínicos/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Demografia , Feminino , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , Distribuição de Poisson , Medição de Risco , Escócia , Estatísticas não Paramétricas
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