Comprehensive identification of pleiotropic loci for body fat distribution using the NHGRI‐EBI Catalog of published genome‐wide association studies

2018 ◽  
Vol 20 (3) ◽  
pp. 385-406 ◽  
Author(s):  
Yuvreet Kaur ◽  
Dominic X. Wang ◽  
Hsin‐Yen Liu ◽  
David Meyre
Keyword(s):  
Body Fat ◽  
Association Studies ◽  
Fat Distribution ◽  
Body Fat Distribution ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry

2018 ◽  
Vol 28 (1) ◽  
pp. 166-174 ◽  
Author(s):  
Sara L Pulit ◽  
Charli Stoneman ◽  
Andrew P Morris ◽  
Andrew R Wood ◽  
Craig A Glastonbury ◽  
...  
Keyword(s):  
Body Fat ◽  
Association Studies ◽  
Meta Analysis ◽  
Fat Distribution ◽  
Body Fat Distribution ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
A Genome

Abstract More than one in three adults worldwide is either overweight or obese. Epidemiological studies indicate that the location and distribution of excess fat, rather than general adiposity, are more informative for predicting risk of obesity sequelae, including cardiometabolic disease and cancer. We performed a genome-wide association study meta-analysis of body fat distribution, measured by waist-to-hip ratio (WHR) adjusted for body mass index (WHRadjBMI), and identified 463 signals in 346 loci. Heritability and variant effects were generally stronger in women than men, and we found approximately one-third of all signals to be sexually dimorphic. The 5% of individuals carrying the most WHRadjBMI-increasing alleles were 1.62 times more likely than the bottom 5% to have a WHR above the thresholds used for metabolic syndrome. These data, made publicly available, will inform the biology of body fat distribution and its relationship with disease.

scholarly journals Genome-Wide Association Study of Body Fat Distribution identifies Novel Adiposity Loci and Sex-Specific Genetic Effects

2017 ◽  
Author(s):  
Mathias Rask-Andersen ◽  
Torgny Karlsson ◽  
Weronica E Ek ◽  
Åsa Johansson
Keyword(s):  
Body Fat ◽  
Genome Wide Association Study ◽  
Metabolic Diseases ◽  
Association Studies ◽  
Fat Distribution ◽  
Body Fat Distribution ◽  
The Body ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

Body mass and body fat composition are of clinical interest due to their links to cardiovascular- and metabolic diseases. Fat stored in the trunk has been suggested as more pathogenic compared to fat stored in other compartments of the body. In this study, we performed genome-wide association studies (GWAS) for the proportion of body fat distributed to the arms, legs and trunk estimated from segmental bio-electrical impedance analysis (sBIA) for 362,499 individuals from the UK Biobank. A total of 97 loci, were identified to be associated with body fat distribution, 40 of which have not previously been associated with an anthropometric trait. A high degree of sex-heterogeneity was observed and associations were primarily observed in females, particularly for distribution of fat to the legs or trunk. Our findings also implicate that body fat distribution in females involves mesenchyme derived tissues and cell types, female endocrine tissues a well as several enzymatically active members of the ADAMTS family of metalloproteinases, which are involved in extracellular matrix maintenance and remodeling.

scholarly journals Meta-analysis of genome-wide association studies for body fat distribution in 694,649 individuals of European ancestry

2018 ◽  
Author(s):  
Sara L. Pulit ◽  
Charli Stoneman ◽  
Andrew P. Morris ◽  
Andrew R. Wood ◽  
Craig A. Glastonbury ◽  
...  
Keyword(s):  
Body Fat ◽  
Association Studies ◽  
Meta Analysis ◽  
Fat Distribution ◽  
Body Fat Distribution ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
A Genome

AbstractOne in four adults worldwide are either overweight or obese. Epidemiological studies indicate that the location and distribution of excess fat, rather than general adiposity, is most informative for predicting risk of obesity sequellae, including cardiometabolic disease and cancer. We performed a genome-wide association study meta-analysis of body fat distribution, measured by waist-to-hip ratio adjusted for BMI (WHRadjBMI), and identified 463 signals in 346 loci. Heritability and variant effects were generally stronger in women than men, and we found approximately one-third of all signals to be sexually dimorphic. The 5% of individuals carrying the most WHRadjBMI-increasing alleles were 1.62 times more likely than the bottom 5% to have a WHR above the thresholds used for metabolic syndrome. These data, made publicly available, will inform the biology of body fat distribution and its relationship with disease.

Abstract 22: Influence of Smoking and Sex on Genetic Associations of Body Fat Distribution: The Giant (Genetic Investigation of ANthropometric Traits) Consortium

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Kristin L Young ◽  
David Hadley ◽  
Anne Justice ◽  
Thomas Winkler ◽  
Misa Graff ◽  
...  
Keyword(s):  
Body Fat ◽  
Genetic Variants ◽  
Fixed Effects ◽  
Smoking Status ◽  
Association Studies ◽  
Fat Distribution ◽  
Body Fat Distribution ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Main Effects

Visceral fat and smoking are important risk factors for CVD and other long-term poor health outcomes. Central adiposity is frequently assessed in population studies using waist-to-hip ratio adjusted for BMI (WHRadjBMI). Genome-wide association studies (GWAS) have discovered loci that influence WHRadjBMI, sometimes with sex-specific effects. However, we do not know whether and how smoking behavior influences the association between genetic variants and WHRadjBMI. Our study investigates the influence of smoking and genetic variants on WHRadjBMI, with particular consideration for differential effects by sex. Forty-one GIANT GWAS (108,397 participants) were used to investigate the influence of smoking on SNP WHRadjBMI associations using sex-stratified models considering SNP main effects adjusted for smoking status, and SNP main effects stratified by smoking status. Results from each study were meta-analyzed using an inverse-variance weighted fixed-effects model for men and women separately as well as combined. A total of 19 SNPs reached genome-wide significance (p<5x10-8) having adjusted the SNP effect for smoking across strata (women, men, and combined), including 11 previously reported WHRadjBMI loci. For known WHRadjBMI loci, the influence of smoking varied by sex. In women, four known WHRadjBMI SNPs (TBX15, DNM3, RSPO3, and ADAMTS9) had a greater effect in smokers vs. nonsmokers (TBX15: β(SE) = 0.0506 (0.014), p = 3.84x10-4) vs. β(SE) = 0.0382 (0.0072), p = 1.14x10-7). Three of these (TBX15, DNM3, RSPO3) have been previously associated with tobacco use disorder (TUD). In men, three known WHRadjBMI loci (ADAMTS9, DNM3, ZNRF3) had a greater effect among smokers vs nonsmokers (ZNRF3: β(SE) = 0.0365 (0.0148), p = 1.37x10-2) vs β(SE) = 0.0192 (0.0088), p = 12.87x10-2). Eight of our 19 top SNPs have not been previously associated with WHRadjBMI (within 500 kb). Of these eight loci, distinct patterns of association by smoking and sex were again noted. In addition, one locus (ABCA1) has been previously associated with TUD. In addition to identifying novel loci associated with body fat distribution, these findings underscore the importance of considering the effect of smoking when investigating the genetics of obesity related phenotypes and emphasize the need to consider sex separately when studying the effects of smoking on body fat distribution.

scholarly journals Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci

PLoS Genetics ◽  
2013 ◽  
Vol 9 (8) ◽  
pp. e1003681 ◽  
Author(s):  
Ching-Ti Liu ◽  
Keri L. Monda ◽  
Kira C. Taylor ◽  
Leslie Lange ◽  
Ellen W. Demerath ◽  
...  
Keyword(s):  
Body Fat ◽  
African Ancestry ◽  
Fat Distribution ◽  
Body Fat Distribution ◽  
Genome Wide Association ◽  
Genome Wide

scholarly journals Genetics of Body Fat Distribution: Comparative Analyses in Populations with European, Asian and African Ancestries

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 841
Author(s):  
Chang Sun ◽  
Peter Kovacs ◽  
Esther Guiu-Jurado
Keyword(s):  
Candidate Genes ◽  
Body Fat ◽  
Current Knowledge ◽  
Association Studies ◽  
Fat Distribution ◽  
Body Fat Distribution ◽  
Genome Wide Association Studies ◽  
Metabolic Complications ◽  
Asian Populations ◽  
European Populations

Preferential fat accumulation in visceral vs. subcutaneous depots makes obese individuals more prone to metabolic complications. Body fat distribution (FD) is regulated by genetics. FD patterns vary across ethnic groups independent of obesity. Asians have more and Africans have less visceral fat compared with Europeans. Consequently, Asians tend to be more susceptible to type 2 diabetes even with lower BMIs when compared with Europeans. To date, genome-wide association studies (GWAS) have identified more than 460 loci related to FD traits. However, the majority of these data were generated in European populations. In this review, we aimed to summarize recent advances in FD genetics with a focus on comparisons between European and non-European populations (Asians and Africans). We therefore not only compared FD-related susceptibility loci identified in three ethnicities but also discussed whether known genetic variants might explain the FD pattern heterogeneity across different ancestries. Moreover, we describe several novel candidate genes potentially regulating FD, including NID2, HECTD4 and GNAS, identified in studies with Asian populations. It is of note that in agreement with current knowledge, most of the proposed FD candidate genes found in Asians belong to the group of developmental genes.

scholarly journals A Genome-Wide Association Study of Novel Genetic Variants Associated With Anthropometric Traits in Koreans

2021 ◽  
Vol 12 ◽  
Author(s):  
Hye-Won Cho ◽  
Hyun-Seok Jin ◽  
Yong-Bin Eom
Keyword(s):  
Genetic Variants ◽  
Genetic Factors ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Fat Distribution ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
A Genome

Most previous genome-wide association studies (GWAS) have identified genetic variants associated with anthropometric traits. However, most of the evidence were reported in European populations. Anthropometric traits such as height and body fat distribution are significantly affected by gender and genetic factors. Here we performed GWAS involving 64,193 Koreans to identify the genetic factors associated with anthropometric phenotypes including height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip ratio. We found nine novel single-nucleotide polymorphisms (SNPs) and 59 independent genetic signals in genomic regions that were reported previously. Of the 19 SNPs reported previously, eight genetic variants at RP11-513I15.6 and one genetic variant at the RP11-977G19.10 region and six Asian-specific genetic variants were newly found. We compared our findings with those of previous studies in other populations. Five overlapping genetic regions (PAN2, ANKRD52, RNF41, HGMA1, and C6orf106) had been reported previously but none of the SNPs were independently identified in the current study. Seven of the nine newly found novel loci associated with height in women revealed a statistically significant skeletal expression of quantitative trait loci. Our study provides additional insight into the genetic effects of anthropometric phenotypes in East Asians.

scholarly journals Sexual dimorphisms in genetic loci linked to body fat distribution

2017 ◽  
Vol 37 (1) ◽  
Author(s):  
Sara L. Pulit ◽  
Tugce Karaderi ◽  
Cecilia M. Lindgren
Keyword(s):  
Sexual Dimorphism ◽  
Body Fat ◽  
Association Studies ◽  
Genetic Regulation ◽  
Fat Distribution ◽  
Body Fat Distribution ◽  
Genome Wide Association Studies ◽  
Genetic Loci ◽  
Fat Percentage ◽  
Total Fat

Obesity is a chronic condition associated with increased morbidity and mortality and is a risk factor for a number of other diseases including type 2 diabetes and cardiovascular disease. Obesity confers an enormous, costly burden on both individuals and public health more broadly. Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes. Body fat distribution is distinct from overall obesity in measurement, but studies of body fat distribution can yield insights into the risk factors for and causes of overall obesity. Sexual dimorphism in body fat distribution is present throughout life. Though sexual dimorphism is subtle in early stages of life, it is attenuated in puberty and during menopause. This phenomenon could be, at least in part, due to the influence of sex hormones on the trait. Findings from recent large genome-wide association studies (GWAS) for various measures of body fat distribution (including waist-to-hip ratio, hip or waist circumference, trunk fat percentage and the ratio of android and gynoid fat percentage) emphasize the strong sexual dimorphism in the genetic regulation of fat distribution traits. Importantly, sexual dimorphism is not observed for overall obesity (as assessed by body mass index or total fat percentage). Notably, the genetic loci associated with body fat distribution, which show sexual dimorphism, are located near genes that are expressed in adipose tissues and/or adipose cells. Considering the epidemiological and genetic evidence, sexual dimorphism is a prominent feature of body fat distribution. Research that specifically focuses on sexual dimorphism in fat distribution can provide novel insights into human physiology and into the development of obesity and its comorbidities, as well as yield biological clues that will aid in the improvement of disease prevention and treatment.

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