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

2010 ◽  
Vol 13 (2) ◽  
pp. 179-193 ◽  
Author(s):  
Jimmy Z. Liu ◽  
Sarah E. Medland ◽  
Margaret J. Wright ◽  
Anjali K. Henders ◽  
Andrew C. Heath ◽  
...  

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.

2018 ◽  
Vol 27 (20) ◽  
pp. 3641-3649 ◽  
Author(s):  
Loic Yengo ◽  
Julia Sidorenko ◽  
Kathryn E Kemper ◽  
Zhili Zheng ◽  
Andrew R Wood ◽  
...  

2020 ◽  
Vol 34 (5) ◽  
pp. 524-531 ◽  
Author(s):  
Sophie E ter Hark ◽  
Stéphane Jamain ◽  
Dick Schijven ◽  
Bochao D Lin ◽  
Mark K Bakker ◽  
...  

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.


PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246436
Author(s):  
Zhaoying Li ◽  
Weijing Wang ◽  
Xiaocao Tian ◽  
Haiping Duan ◽  
Chunsheng Xu ◽  
...  

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.


Gene ◽  
2012 ◽  
Vol 500 (1) ◽  
pp. 80-84 ◽  
Author(s):  
Ke-Sheng Wang ◽  
Xuefeng Liu ◽  
Shimin Zheng ◽  
Min Zeng ◽  
Yue Pan ◽  
...  

2015 ◽  
Author(s):  
Andrew R Wood ◽  
Jessica Tyrell ◽  
Robin Beaumont ◽  
Samuel E Jones ◽  
Marcus A Tuke ◽  
...  

Genome-wide association studies have identified hundreds of common genetic variants associated with obesity and Type 2 diabetes. These studies have focused on additive association tests. Identifying deviations from additivity may provide new biological insights and explain some of the missing heritability for these diseases. To identify non-additive associations we performed a genome-wide association study using a dominance deviation model for BMI, obesity and Type 2 diabetes (4,040 cases) in 120,286 individuals of British ancestry from the UK Biobank study. Known obesity-associated variants in FTO showed strong evidence for deviation from additivity (P=3x10-5) through a recessive effect of the BMI-increasing allele. The average BMI of individuals carrying 0, 1 or 2 BMI-raising alleles was 27.27kg/m2 (95% CI:27.22-27.31), 27.54kg/m2 (95% CI:27.50-27.58), and 28.07kg/m2 (95% CI:28.0-28.14), respectively. A similar effect was observed in 105,643 individuals from the GIANT consortium (P=0.003; Pmeta-analysis=1x10-7). We also detected a recessive effect (Pdomdev=5x10-4) at CDKAL1 for Type 2 diabetes risk. Homozygous risk allele carriers had an OR=1.48 (95% CI:1.32-1.65) in comparison to the heterozygous group that had an OR=1.06 (95% CI:0.99-1.14), a result consistent with a previous study. We did not identify any novel genome-wide associations. In conclusion, although we find no evidence for widespread non-additive effects contributing to the genetic risk of obesity and Type 2 diabetes, we find robust examples of recessive effects at the FTO and CDKAL1 loci.


PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e105062 ◽  
Author(s):  
Molly Scannell Bryan ◽  
Maria Argos ◽  
Brandon Pierce ◽  
Lin Tong ◽  
Muhammad Rakibuz-Zaman ◽  
...  

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