A novel locus for body mass index on 5p15.2: A meta-analysis of two genome-wide association studies

Genome-wide association studies (GWAS) stand as powerful experimental designs for identifying DNA variants associated with complex traits and diseases. In the past decade, both the number of such studies and their sample sizes have increased dramatically. Recent GWAS of height and body mass index (BMI) in ∼250,000 European participants have led to the discovery of ∼700 and ∼100 nearly independent SNPs associated with these traits, respectively. Here we combine summary statistics from those two studies with GWAS of height and BMI performed in ∼450,000 UK Biobank participants of European ancestry. Overall, our combined GWAS meta-analysis reaches N∼700,000 individuals and substantially increases the number of GWAS signals associated with these traits. We identified 3,290 and 716 near-independent SNPs associated with height and BMI, respectively (at a revised genome-wide significance threshold of p<1 × 10−8), including 1,185 height-associated SNPs and 554 BMI-associated SNPs located within loci not previously identified by these two GWAS. The genome-wide significant SNPs explain ∼24.6% of the variance of height and ∼5% of the variance of BMI in an independent sample from the Health and Retirement Study (HRS). Correlations between polygenic scores based upon these SNPs with actual height and BMI in HRS participants were 0.44 and 0.20, respectively. From analyses of integrating GWAS and eQTL data by Summary-data based Mendelian Randomization (SMR), we identified an enrichment of eQTLs amongst lead height and BMI signals, prioritisting 684 and 134 genes, respectively. Our study demonstrates that, as previously predicted, increasing GWAS sample sizes continues to deliver, by discovery of new loci, increasing prediction accuracy and providing additional data to achieve deeper insight into complex trait biology. All summary statistics are made available for follow up studies.

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Genome-Wide Association Study of Height and Body Mass Index in Australian Twin Families

Twin Research and Human Genetics ◽

10.1375/twin.13.2.179 ◽

2010 ◽

Vol 13 (2) ◽

pp. 179-193 ◽

Cited By ~ 40

Author(s):

Jimmy Z. Liu ◽

Sarah E. Medland ◽

Margaret J. Wright ◽

Anjali K. Henders ◽

Andrew C. Heath ◽

...

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Genome Wide Association Study ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Single Genome ◽

Common Genetic Variants ◽

Twin Families

AbstractHuman height and body mass index are influenced by a large number of genes, each with small effects, along with environment. To identify common genetic variants associated with these traits, we performed genome-wide association studies in 11,536 individuals composed of Australian twins, family members, and unrelated individuals at ∼550,000 genotyped SNPs. We identified a single genome-wide significant variant for height (Pvalue = 1.06 × 10–9) located inHHIP, a well-replicated height-associated gene. Suggestive levels of association were found for other known genes associated with height (Pvalues < 1 × 10–6):ADAMTSL3,EFEMP1,GPR126, andHMGA2; and BMI (Pvalues < 1 × 10–4):FTOandMC4R. Together, these variants explain less than 2% of total phenotypic variation for height and 0.5% for BMI.

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Genome-wide association studies of body mass index

Genome-Wide Association Studies ◽

10.1017/cbo9781107337459.007 ◽

2015 ◽

pp. 69-78

Author(s):

Tuomas O. Kilpeläinen

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genome Wide

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A new genetic locus for antipsychotic-induced weight gain: A genome-wide study of first-episode psychosis patients using amisulpride (from the OPTiMiSE cohort)

Journal of Psychopharmacology ◽

10.1177/0269881120907972 ◽

2020 ◽

Vol 34 (5) ◽

pp. 524-531 ◽

Cited By ~ 1

Author(s):

Sophie E ter Hark ◽

Stéphane Jamain ◽

Dick Schijven ◽

Bochao D Lin ◽

Mark K Bakker ◽

...

Keyword(s):

Body Mass Index ◽

Weight Gain ◽

Body Mass ◽

Association Studies ◽

Genome Wide Association ◽

Chromatin Interaction ◽

First Episode ◽

Genome Wide Association Studies ◽

Genome Wide ◽

A Genome

Background: Antipsychotic-induced weight gain is a common and debilitating side effect of antipsychotics. Although genome-wide association studies of antipsychotic-induced weight gain have been performed, few genome-wide loci have been discovered. Moreover, these genome-wide association studies have included a wide variety of antipsychotic compounds. Aims: We aim to gain more insight in the genomic loci affecting antipsychotic-induced weight gain. Given the variable pharmacological properties of antipsychotics, we hypothesized that targeting a single antipsychotic compound would provide new clues about genomic loci affecting antipsychotic-induced weight gain. Methods: All subjects included for this genome-wide association study ( n=339) were first-episode schizophrenia spectrum disorder patients treated with amisulpride and were minimally medicated (defined as antipsychotic use <2 weeks in the previous year and/or <6 weeks lifetime). Weight gain was defined as the increase in body mass index from before until approximately 1 month after amisulpride treatment. Results: Our genome-wide association analyses for antipsychotic-induced weight gain yielded one genome-wide significant hit (rs78310016; β=1.05; p=3.66 × 10−08; n=206) in a locus not previously associated with antipsychotic-induced weight gain or body mass index. Minor allele carriers had an odds ratio of 3.98 ( p=1.0 × 10−03) for clinically meaningful antipsychotic-induced weight gain (⩾7% of baseline weight). In silico analysis elucidated a chromatin interaction with 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1. In an attempt to replicate single-nucleotide polymorphisms previously associated with antipsychotic-induced weight gain, we found none were associated with amisulpride-induced weight gain. Conclusion: Our findings suggest the involvement of rs78310016 and possibly 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 in antipsychotic-induced weight gain. In line with the unique binding profile of this atypical antipsychotic, our findings furthermore hint that biological mechanisms underlying amisulpride-induced weight gain differ from antipsychotic-induced weight gain by other atypical antipsychotics.

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Bivariate genome-wide association study (GWAS) of body mass index and blood pressure phenotypes in northern Chinese twins

PLoS ONE ◽

10.1371/journal.pone.0246436 ◽

2021 ◽

Vol 16 (2) ◽

pp. e0246436

Author(s):

Zhaoying Li ◽

Weijing Wang ◽

Xiaocao Tian ◽

Haiping Duan ◽

Chunsheng Xu ◽

...

Keyword(s):

Blood Pressure ◽

Body Mass Index ◽

Body Mass ◽

Genetic Variants ◽

Quantitative Trait ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Northern Chinese

Recently, new loci related to body mass index (BMI) or blood pressure (BP) have been identified respectively in genome-wide association studies (GWAS). However, limited studies focused on jointly associated genetic variance between systolic pressure (SBP), diastolic pressure (DBP) and BMI. Therefore, a bivariate twin study was performed to explore the genetic variants associated with BMI-SBP, BMI-DBP and SBP-DBP. A total of 380 twin pairs (137 dizygotic pairs and 243 monozygotic pairs) recruited from Qingdao Twin Registry system were used to access the genetic correlations (0.2108 for BMI-SBP, 0.2345 for BMI-DBP, and 0.6942 for SBP-DBP, respectively) by bivariate Cholesky decomposition model. Bivariate GWAS in 137 dizygotic pairs nominated 27 single identified 27 quantitative trait nucleotides (QTNs) for BMI and SBP, 27 QTNs for BMI and DBP, and 25 QTNs for SBP and DBP with the suggestive P-value threshold of 1×10−5. After imputation, we found eight SNPs, one for both BMI-SBP and SBP-DBP, and eight for SBP-DBP, exceed significant statistic level. Expression quantitative trait loci analysis identified rs4794029 as new significant eQTL in tissues related to BMI and SBP. Also, we found 6 new significant eQTLs (rs4400367, rs10113750, rs11776003, rs3739327, rs55978930, and rs4794029) in tissues were related to SBP and DBP. Gene-based analysis identified nominally associated genes (P < 0.05) with BMI-SBP, BMI-DBP, and SBP-DBP, respectively, such as PHOSPHO1, GNGT2, KEAP1, and S1PR5. In the pathway analysis, we found some pathways associated with BMI-SBP, BMI-DBP and SBP-DBP, such as prion diseases, IL5 pathway, cyclin E associated events during G1/S transition, TGF beta signaling pathway, G βγ signaling through PI3Kγ, prolactin receptor signaling etc. These findings may enrich the results of genetic variants related to BMI and BP traits, and provide some evidences to future study the pathogenesis of hypertension and obesity in the northern Chinese population.

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