Novel recessive locus for body mass index in childhood asthma

Most genome-wide association studies of obesity and body mass index (BMI) have so far assumed an additive mode of inheritance in their analysis, although association testing supports a recessive effect for some of the established loci, for example, rs1421085 in FTO. In two whole-genome sequencing (WGS) studies of children with asthma and their parents (892 Costa Rican trios and 286 North American trios), we discovered an association between a locus (rs9292139) in LOC102724122 and BMI that reaches genome-wide significance under a recessive model in the combined analysis. As the association does not achieve significance under an additive model, our finding illustrates the benefits of the recessive model in WGS analyses.

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Meta-analysis of genome-wide association studies for height and body mass index in ∼700000 individuals of European ancestry

Human Molecular Genetics ◽

10.1093/hmg/ddy271 ◽

2018 ◽

Vol 27 (20) ◽

pp. 3641-3649 ◽

Cited By ~ 401

Author(s):

Loic Yengo ◽

Julia Sidorenko ◽

Kathryn E Kemper ◽

Zhili Zheng ◽

Andrew R Wood ◽

...

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Association Studies ◽

Meta Analysis ◽

Genome Wide Association ◽

European Ancestry ◽

Genome Wide Association Studies ◽

Genome Wide

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Quantifying genetic heterogeneity between continental populations for human height and body mass index

Scientific Reports ◽

10.1038/s41598-021-84739-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jing Guo ◽

Andrew Bakshi ◽

Ying Wang ◽

Longda Jiang ◽

Loic Yengo ◽

...

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Complex Traits ◽

Association Studies ◽

Significant Snps ◽

Complex Trait ◽

European Ancestry ◽

Genome Wide Association Studies ◽

Population Difference ◽

Genome Wide

AbstractGenome-wide association studies (GWAS) in samples of European ancestry have identified thousands of genetic variants associated with complex traits in humans. However, it remains largely unclear whether these associations can be used in non-European populations. Here, we seek to quantify the proportion of genetic variation for a complex trait shared between continental populations. We estimated the between-population correlation of genetic effects at all SNPs ($$r_{g}$$ r g ) or genome-wide significant SNPs ($$r_{{g\left( {GWS} \right)}}$$ r g GWS ) for height and body mass index (BMI) in samples of European (EUR; $$n = 49,839$$ n = 49 , 839 ) and African (AFR; $$n = 17,426$$ n = 17 , 426 ) ancestry. The $$\hat{r}_{g}$$ r ^ g between EUR and AFR was 0.75 ($${\text{s}}.{\text{e}}. = 0.035$$ s . e . = 0.035 ) for height and 0.68 ($${\text{s}}.{\text{e}}. = 0.062$$ s . e . = 0.062 ) for BMI, and the corresponding $$\hat{r}_{{g\left( {GWS} \right)}}$$ r ^ g GWS was 0.82 ($${\text{s}}.{\text{e}}. = 0.030$$ s . e . = 0.030 ) for height and 0.87 ($${\text{s}}.{\text{e}}. = 0.064$$ s . e . = 0.064 ) for BMI, suggesting that a large proportion of GWAS findings discovered in Europeans are likely applicable to non-Europeans for height and BMI. There was no evidence that $$\hat{r}_{g}$$ r ^ g differs in SNP groups with different levels of between-population difference in allele frequency or linkage disequilibrium, which, however, can be due to the lack of power.

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Quantifying genetic heterogeneity between continental populations for human height and body mass index

10.1101/839373 ◽

2019 ◽

Cited By ~ 2

Author(s):

Jing Guo ◽

Andrew Bakshi ◽

Ying Wang ◽

Longda Jiang ◽

Loic Yengo ◽

...

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Complex Traits ◽

Association Studies ◽

Significant Snps ◽

Complex Trait ◽

European Ancestry ◽

Genome Wide Association Studies ◽

Population Difference ◽

Genome Wide

AbstractGenome-wide association studies (GWAS) in samples of European ancestry have identified thousands of genetic variants associated with complex traits in humans. However, it remains largely unclear whether these associations can be used in non-European populations. Here, we seek to quantify the proportion of genetic variation for a complex trait shared between continental populations. We estimated the between-population correlation of genetic effects at all SNPs (rg) or genome-wide significant SNPs (rg(GWS)) for height and body mass index (BMI) in samples of European (EUR; n = 49,839) and African (AFR; n = 17,426) ancestry. The between EUR and AFR was 0.75 (s. e. = 0.035) for height and 0.68 (s. e. = 0.062) for BMI, and the corresponding was 0.82 (s. e. = 0.030) for height and 0.87 (s. e. = 0.064) for BMI, suggesting that a large proportion of GWAS findings discovered in Europeans are likely applicable to non-Europeans for height and BMI. There was no evidence that differs in SNP groups with different levels of between-population difference in allele frequency or linkage disequilibrium, which, however, can be due to the lack of power.

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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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