Population genetic differentiation of height and body mass index across Europe.
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ABSTRACT:
SUBMITTER: Robinson MR
PROVIDER: S-EPMC4984852 | biostudies-literature | 2015 Nov
REPOSITORIES: biostudies-literature
Publications
Population genetic differentiation of height and body mass index across Europe.
Robinson Matthew R MR Hemani Gibran G Medina-Gomez Carolina C Mezzavilla Massimo M Esko Tonu T Shakhbazov Konstantin K Powell Joseph E JE Vinkhuyzen Anna A Berndt Sonja I SI Gustafsson Stefan S Justice Anne E AE Kahali Bratati B Locke Adam E AE Pers Tune H TH Vedantam Sailaja S Wood Andrew R AR van Rheenen Wouter W Andreassen Ole A OA Gasparini Paolo P Metspalu Andres A Berg Leonard H van den LH Veldink Jan H JH Rivadeneira Fernando F Werge Thomas M TM Abecasis Goncalo R GR Boomsma Dorret I DI Chasman Daniel I DI de Geus Eco J C EJ Frayling Timothy M TM Hirschhorn Joel N JN Hottenga Jouke Jan JJ Ingelsson Erik E Loos Ruth J F RJ Magnusson Patrik K E PK Martin Nicholas G NG Montgomery Grant W GW North Kari E KE Pedersen Nancy L NL Spector Timothy D TD Speliotes Elizabeth K EK Goddard Michael E ME Yang Jian J Visscher Peter M PM
Nature genetics 20150914 11
Across-nation differences in the mean values for complex traits are common, but the reasons for these differences are unknown. Here we find that many independent loci contribute to population genetic differences in height and body mass index (BMI) in 9,416 individuals across 14 European countries. Using discovery data on over 250,000 individuals and unbiased effect size estimates from 17,500 sibling pairs, we estimate that 24% (95% credible interval (CI) = 9%, 41%) and 8% (95% CI = 4%, 16%) of t ...[more]
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Project description:ObjectiveTo analyze the associations between height and BMI categories in a Portuguese representative sample.MethodsThis is a cross-sectional study with a representative sample of 32,644 Portuguese adults (52.4% females). Sociodemographic and lifestyle characteristics were obtained along with self-reported height and weight. We performed generalized linear models to assess the differences in attained height across BMI categories; analyses were adjusted for age, gender, education, family income per month, proxy reporting information, dietary patterns, and smoking.ResultsBMI categories included underweight and normal weight (46.4%), overweight (37.6%), obese class I and II (15.2%), and obese class III (0.8%). Adults with normal weight had a significantly higher height (females +7 cm and males +5 cm) when compared to obese class III. As BMI categories increased, height decreased. In females and males, after adjusting for confounders, estimates of attained height decreased when compared to the unadjusted model (? = -0.049, 95% CI = -0.050; -0.049 and ? = -0.030, 95% CI = -0.031; -0.029, respectively), although they remained still significant.ConclusionOur results suggest a significant difference in attained height between BMI categories. Future intervention programs aiming at preventing overweight and obesity should monitor sociodemographic, health and environmental conditions that affect attained height potential.
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Project description:BackgroundAlthough excess body weight has been associated with cancers of the gastric cardia, relationships with gastric cancer at other anatomic subsites are not well defined. Furthermore, subsite-specific associations with attained height have not been fully assessed.MethodsIn 1995-1996, 483,700 Whites enrolling in the multi-state NIH-AARP Diet and Health Study self-reported height and weight. Gastric cancers occurring through 31 December 2006 were ascertained from regional population-based registries. We used Cox regression models to estimate cancer hazard ratios (HRs) for sex-specific tertiles of height and weight and for body mass index (BMI) categories of the World Health Organization.ResultsOne thousand incident cancers (48 % localized to the cardia, 4 % fundus, 6 % corpus, 3 % greater curvature, 6 % lesser curvature, 10 % antrum, 2 % pylorus, 5 % overlapping lesion, and 16 % unspecified) occurred an average of 5.4 years after enrollment. After controlling for effects of age, sex, education, and smoking, we found an inverse association between height and total noncardia cancers (i.e., fundus, corpus, greater and lesser curvatures, antrum, and pylorus), with HRs vs. tertile 1 of 0.65 and 0.71 for tertiles 2 and 3, respectively (p trend = 0.016). Trends were consistent for individual noncardia subsites. In contrast, although weight and BMI were each associated with risk of cardia cancer, neither was associated with total noncardia cancer nor individual subsites.ConclusionNoncardia gastric cancer is associated with short stature but not with high body weight or obesity. The excess risk for shorter adults would be consistent with the known association of chronic H. pylori infection with growth retardation during childhood.
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Project description:BackgroundChildren with familial dysautonomia (FD) are smaller and grow more slowly than the general population. It is unknown whether this abnormal growth is due to comorbidities that patients with FD live with, or if it is a direct effect of the disease-causing homozygous ELP-1 mutations. Here, we created growth curves for weight, height, and body mass index (BMI) in male and female children with FD to monitor the nutritional status of patients with FD.MethodsWe used the New York University (NYU) FD Registry which includes data from 680 individuals with FD who were followed longitudinally since birth. We generated sex-specific FD growth charts for three age ranges (birth to 36 months, 2 to 20 years, and 2 to 40 years) and compared them to the general population. We generated Kaplan-Meier curves to test the hypothesis that FD patients with low BMI had shorter survival than the rest of the cohort.ResultsGrowth charts generated from 591 individuals with FD show that these patients grow more slowly, reach less height, and gain less weight than the general population. The impact of FD on height was more pronounced in girls than in boys. However, both groups showed markedly low weights, which resulted in low BMI. Low weight, but not height, is already evident at birth. In a subpopulation of FD patients, we found that treatment with growth hormone or spinal fusion surgery helped patients achieve the expected growth characteristic of FD patients, but these treatments did not lead FD patients to achieve the growth pattern of the general population. Contrary to our hypothesis, low BMI had no impact on patient survival.ConclusionsPediatric patients with FD have lower height, weight, and BMI compared to the general pediatric population, but this does not appear to affect survival. Growth curves specific to the FD population are an important tool to monitor growth and nutritional status in pediatric patients with FD when the general population growth curves are of limited use.
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Project description:We propose a method (GREML-LDMS) to estimate heritability for human complex traits in unrelated individuals using whole-genome sequencing data. We demonstrate using simulations based on whole-genome sequencing data that ?97% and ?68% of variation at common and rare variants, respectively, can be captured by imputation. Using the GREML-LDMS method, we estimate from 44,126 unrelated individuals that all ?17 million imputed variants explain 56% (standard error (s.e.) = 2.3%) of variance for height and 27% (s.e. = 2.5%) of variance for body mass index (BMI), and we find evidence that height- and BMI-associated variants have been under natural selection. Considering the imperfect tagging of imputation and potential overestimation of heritability from previous family-based studies, heritability is likely to be 60-70% for height and 30-40% for BMI. Therefore, the missing heritability is small for both traits. For further discovery of genes associated with complex traits, a study design with SNP arrays followed by imputation is more cost-effective than whole-genome sequencing at current prices.
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Project description:ObjectivesAdult body mass (MB) empirically scales as height (Ht) squared (MB ∝ Ht(2) ), but does regional body mass and body composition as a whole also scale as Ht(2) ? This question is relevant to a wide range of biological topics, including interpretation of body mass index (BMI).MethodsDual-energy X-ray absorptiometry (DXA) was used to quantify regional body mass [head (MH), trunk, arms, and legs] and whole-body composition [fat, lean soft tissue (LST), and bone mineral content (BMC)] in non-Hispanic (NH) white, NH black, Mexican American, and Korean adults participating in the National Health and Nutrition Examination Survey (NHANES; n = 17,126) and Korean NHANES (n = 8,942). Regression models were developed to establish Ht scaling powers for each measured component with adjustments for age and adiposity.ResultsExploratory analyses revealed a consistent scaling pattern across men and women of the four population groups: regional mass powers, head (∼0.8-1) < arms and trunk (∼1.8-2.3) < legs (∼2.3-2.6); and body composition, LST (∼2.0-2.3) < BMC (∼2.1-2.4). Small sex and population differences in scaling powers were also observed. As body mass scaled uniformly across the eight sex and population groups as Ht(∼2) , tall and short subjects differed in body shape (e.g., MH/MB ∝ Ht(-∼1) ) and composition.ConclusionsAdult human body shape and relative composition are a function of body size as represented by stature, a finding that reveals a previously unrecognized phenotypic heterogeneity as defined by BMI. These observations provide new pathways for exploring mechanisms governing the interrelations between adult stature, body morphology, biomechanics, and metabolism.
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Project description:BackgroundHeight and body mass index (BMI) have both been positively associated with melanoma risk, although findings for BMI have been less consistent than height. It remains unclear, however, whether these associations reflect causality or are due to residual confounding by environmental and lifestyle risk factors. We re-evaluated these associations using a two-sample Mendelian randomization (MR) approach.MethodsWe identified single nucleotide polymorphisms (SNPs) for BMI and height from separate genome-wide association study (GWAS) meta-analyses. We obtained melanoma SNPs from the most recent melanoma GWAS meta-analysis comprising 12 874 cases and 23 203 controls. We used the inverse variance-weighted estimator to derive separate causal risk estimates across all SNP instruments for BMI and height.ResultsBased on the combined estimate derived from 730 SNPs for BMI, we found no evidence of an association between genetically predicted BMI and melanoma [odds ratio (OR) per one standard deviation (1 SD) (4.6 kg/m2) increase in BMI 1.00, 95% confidence interval (CI): 0.91-1.11]. In contrast, we observed a positive association between genetically-predicted height (derived from a pooled estimate of 3290 SNPs) and melanoma risk [OR 1.08, 95% CI: 1.02-1.13, per 1 SD (9.27 cm) increase in height]. Sensitivity analyses using two alternative MR methods yielded similar results.ConclusionsThese findings provide no evidence for a causal association between higher BMI and melanoma, but support the notion that height is causally associated with melanoma risk. Mechanisms through which height influences melanoma risk remain unclear, and it remains possible that the effect could be mediated through diverse pathways including growth factors and even socioeconomic status.
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Project description:Body mass index (BMI) is a function of weight and height, but changing height has not been emphasized. Using the Framingham Heart Study with 5 decades of data on anthropomorphic measurements and disease states, changing height with age was extracted, and BMI was calculated using current and "young" height (calculated as height at age < 40 years). Decreased height began at age 40, with a mean loss from ages 40 to 80 of 4.8 cm for women and 3.6 cm for men. Using cutoff values of 25 and 30 for overweight and obesity, ~12.5% of women and ~10% of men were misclassified. Comparable figures for obesity classification were ~10 and 8%. At age 70, ~20% of women and ~15% of men were misclassified. Using the BMI corrected to "young" height, obese subjects had an increased risk for developing pre-diabetes and diabetes, with a higher risk for women than men. Using corrected BMI, obese subjects had a higher risk for developing hypertension, lower than for diabetes and higher for men than for women. These data do not establish whether the increased disease risk is clinically important but demonstrate that there is an advantage to using BMI corrected for "young" height when compared with BMI using current age-related height.
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Project description:ObjectiveTo determine whether height and body mass index (BMI) have a causal role in five measures of socioeconomic status.DesignMendelian randomisation study to test for causal effects of differences in stature and BMI on five measures of socioeconomic status. Mendelian randomisation exploits the fact that genotypes are randomly assigned at conception and thus not confounded by non-genetic factors.SettingUK Biobank.Participants119,669 men and women of British ancestry, aged between 37 and 73 years.Main outcome measuresAge completed full time education, degree level education, job class, annual household income, and Townsend deprivation index.ResultsIn the UK Biobank study, shorter stature and higher BMI were observationally associated with several measures of lower socioeconomic status. The associations between shorter stature and lower socioeconomic status tended to be stronger in men, and the associations between higher BMI and lower socioeconomic status tended to be stronger in women. For example, a 1 standard deviation (SD) higher BMI was associated with a £210 (€276; $300; 95% confidence interval £84 to £420; P=6 × 10(-3)) lower annual household income in men and a £1890 (£1680 to £2100; P=6 × 10(-15)) lower annual household income in women. Genetic analysis provided evidence that these associations were partly causal. A genetically determined 1 SD (6.3 cm) taller stature caused a 0.06 (0.02 to 0.09) year older age of completing full time education (P=0.01), a 1.12 (1.07 to 1.18) times higher odds of working in a skilled profession (P=6 × 10(-7)), and a £1130 (£680 to £1580) higher annual household income (P=4 × 10(-8)). Associations were stronger in men. A genetically determined 1 SD higher BMI (4.6 kg/m(2)) caused a £2940 (£1680 to £4200; P=1 × 10(-5)) lower annual household income and a 0.10 (0.04 to 0.16) SD (P=0.001) higher level of deprivation in women only.ConclusionsThese data support evidence that height and BMI play an important partial role in determining several aspects of a person's socioeconomic status, especially women's BMI for income and deprivation and men's height for education, income, and job class. These findings have important social and health implications, supporting evidence that overweight people, especially women, are at a disadvantage and that taller people, especially men, are at an advantage.
| S-EPMC4783516 | biostudies-literature
Project description:BACKGROUND:It is now possible to estimate genetic correlations between two independent samples when there is no overlapping phenotypic information. We applied the latest bivariate genomic methods to children in the UK and older adults in Sweden to ask two questions. Are the same variants driving individual differences in anthropometric traits in these two populations, and are these variants as important in childhood as they are later in life? METHODS:A sample of 3152 11-year-old children in the UK was compared with a sample of 6813 adults with an average age of 65 in Sweden. Genotypes were imputed from 1000 genomes with combined 9?767?136 single nucleotide polymorphisms meeting quality control criteria in both samples. Two cross-sample GCTA-GREML analyses and linkage disequilibrium (LD) score regressions were conducted to assess genetic correlations across more than 50 years: child versus adult height and child versus adult body mass index (BMI). Consistency of effects was tested using the recently proposed polygenic scoring method. RESULTS:For height, GCTA-GREML and LD score indicated strong genetic stability between children and adults, 0.58 (0.16) and 1.335 (1.09), respectively. For BMI, both methods produced similarly strong estimates of genetic stability 0.75 (0.26) and 0.855 (0.49), respectively. In height, adult polygenic score explained 60% of genetic variance in childhood and 10% of variance in BMI. CONCLUSIONS:Here we replicated and extended previous findings of longitudinal genetic stability in anthropometric traits to cross-cultural dimensions, and showed that for height but not BMI these variants are as important in childhood as they are in adulthood.
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