scholarly journals Shared genetic etiology and causality between body fat percentage and cardiovascular diseases: a large-scale genome-wide cross-trait analysis

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhenhuang Zhuang ◽  
Minhao Yao ◽  
Jason Y. Y. Wong ◽  
Zhonghua Liu ◽  
Tao Huang
Keyword(s):  
Cardiovascular Diseases ◽  
Body Fat ◽  
Large Scale ◽  
Genetic Correlations ◽  
Body Fat Percentage ◽  
Fat Percentage ◽  
Genetic Etiology ◽  
Trait Analysis ◽  
Genome Wide ◽  
Shared Genetic

Abstract Background Accumulating evidences have suggested that high body fat percentage (BF%) often occurs in parallel with cardiovascular diseases (CVDs), implying a common etiology between them. However, the shared genetic etiology underlying BF% and CVDs remains unclear. Methods Using large-scale genome-wide association study (GWAS) data, we investigated shared genetics between BF% (N = 100,716) and 10 CVD-related traits (n = 6968-977,323) with linkage disequilibrium score regression, multi-trait analysis of GWAS, and transcriptome-wide association analysis, and evaluated causal associations using Mendelian randomization. Results We found strong positive genetic correlations between BF% and heart failure (HF) (Rg = 0.47, P = 1.27 × 10− 22) and coronary artery disease (CAD) (Rg = 0.22, P = 3.26 × 10− 07). We identified 5 loci and 32 gene-tissue pairs shared between BF% and HF, as well as 16 loci and 28 gene-tissue pairs shared between BF% and CAD. The loci were enriched in blood vessels and brain tissues, while the gene-tissue pairs were enriched in the nervous, cardiovascular, and exo-/endocrine system. In addition, we observed that BF% was causally related with a higher risk of HF (odds ratio 1.63 per 1-SD increase in BF%, P = 4.16 × 10–04) using a MR approach. Conclusions Our findings suggest that BF% and CVDs have shared genetic etiology and targeted reduction of BF% may improve cardiovascular outcomes. This work advances our understanding of the genetic basis underlying co-morbid obesity and CVDs and opens up a new way for early prevention of CVDs.

scholarly journals A large-scale genome-wide association analysis of lung function in the Chinese population identifies novel loci and highlights shared genetic etiology with obesity

2021 ◽  
pp. 2100199
Author(s):  
Zhaozhong Zhu ◽  
Jiachen Li ◽  
Jiahui Si ◽  
Baoshan Ma ◽  
Huwenbo Shi ◽  
...  
Keyword(s):  
Lung Function ◽  
Large Scale ◽  
Causal Effect ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genetic Etiology ◽  
Trait Analysis ◽  
Genome Wide ◽  
Shared Genetic

Lung function is a heritable complex phenotype with obesity being one of its important risk factors. However, the knowledge of their shared genetic basis is limited. Most genome-wide association studies (GWASs) for lung function have been based on European populations, limiting the generalisability across populations. Large-scale lung function GWAS in other populations are lacking.We included 100 285 subjects from China Kadoorie Biobank (CKB). To identify novel loci for lung function, single-trait GWAS were performed on FEV1, FVC, FEV1/FVC in CKB. We then performed genome-wide cross-trait analysis between the lung function and obesity traits (body mass index [BMI], BMI-adjusted waist-to-hip ratio, and BMI-adjusted waist circumference) to investigate the shared genetic effects in CKB. Finally, polygenic risk scores (PRSs) of lung function were developed in CKB and its interaction with BMI's association on lung function were examined. We also conducted cross-trait analysis in parallel with CKB using 457 756 subjects from UK Biobank (UKB) for replication and investigation of ancestry specific effect.We identified 9 genome-wide significant novel loci for FEV1, 6 for FVC and 3 for FEV1/FVC in CKB. FEV1 and FVC showed significant negative genetic correlation with obesity traits in both CKB and UKB. Genetic loci shared between lung function and obesity traits highlighted important pathways, including cell proliferation, embryo and tissue development. Mendelian randomisation analysis suggested significant negative causal effect of BMI on FEV1 and on FVC in both CKB and UKB. Lung function PRSs significantly modified the effect of change-in-BMI on change-in-lung function during an average follow-up of 8 years.This large-scale GWAS of lung function identified novel loci and shared genetic etiology between lung function and obesity. Change-in-BMI might affect change-in-lung function differently according to a subject's polygenic background. These findings may open new avenue for the development of molecular-targeted therapies for obesity and lung function improvement.

scholarly journals Genetic Correlation between Body Fat Percentage and Cardiorespiratory Fitness Suggests Common Genetic Etiology

PLoS ONE ◽  
2016 ◽  
Vol 11 (11) ◽  
pp. e0166738 ◽  
Author(s):  
Theresia M. Schnurr ◽  
Anette P. Gjesing ◽  
Camilla H. Sandholt ◽  
Anna Jonsson ◽  
Yuvaraj Mahendran ◽  
...  
Keyword(s):  
Genetic Correlation ◽  
Cardiorespiratory Fitness ◽  
Body Fat ◽  
Body Fat Percentage ◽  
Fat Percentage ◽  
Genetic Etiology

scholarly journals Shared genetic architecture and casual relationship between leptin levels and type 2 diabetes: large-scale cross-trait meta-analysis and Mendelian randomization analysis

2020 ◽  
Vol 8 (1) ◽  
pp. e001140
Author(s):  
Xinpei Wang ◽  
Jinzhu Jia ◽  
Tao Huang
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Correlation ◽  
Genetic Architecture ◽  
Large Scale ◽  
Meta Analysis ◽  
Genetic Correlations ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Shared Genetic

ObjectiveWe aimed to estimate genetic correlation, identify shared loci and test causality between leptin levels and type 2 diabetes (T2D).Research design and methodsOur study consists of three parts. First, we calculated the genetic correlation of leptin levels and T2D or glycemic traits by using linkage disequilibrium score regression analysis. Second, we conducted a large-scale genome-wide cross-trait meta-analysis using cross-phenotype association to identify shared loci between trait pairs that showed significant genetic correlations in the first part. In the end, we carried out a bidirectional MR analysis to find out whether there is a causal relationship between leptin levels and T2D or glycemic traits.ResultsWe found positive genetic correlations between leptin levels and T2D (Rg=0.3165, p=0.0227), fasting insulin (FI) (Rg=0.517, p=0.0076), homeostasis model assessment-insulin resistance (HOMA-IR) (Rg=0.4785, p=0.0196), as well as surrogate estimates of β-cell function (HOMA-β) (Rg=0.4456, p=0.0214). We identified 12 shared loci between leptin levels and T2D, 1 locus between leptin levels and FI, 1 locus between leptin levels and HOMA-IR, and 1 locus between leptin levels and HOMA-β. We newly identified eight loci that did not achieve genome-wide significance in trait-specific genome-wide association studies. These shared genes were enriched in pancreas, thyroid gland, skeletal muscle, placenta, liver and cerebral cortex. In addition, we found that 1-SD increase in HOMA-IR was causally associated with a 0.329 ng/mL increase in leptin levels (β=0.329, p=0.001).ConclusionsOur results have shown the shared genetic architecture between leptin levels and T2D and found causality of HOMA-IR on leptin levels, shedding light on the molecular mechanisms underlying the association between leptin levels and T2D.

scholarly journals Dissecting the shared genetic architecture of suicide attempt, psychiatric disorders and known risk factors

2020 ◽  
Author(s):  
Niamh Mullins ◽  
Jooeun Kang ◽  
Adrian I Campos ◽  
Jonathan R I Coleman ◽  
Alexis C Edwards ◽  
...  
Keyword(s):  
Risk Factors ◽  
Suicide Attempt ◽  
Psychiatric Disorders ◽  
Risk Taking ◽  
Sleep Disturbances ◽  
Genetic Correlations ◽  
Genetic Etiology ◽  
Genome Wide ◽  
A Genome ◽  
Shared Genetic

AbstractSuicide is a leading cause of death worldwide and non-fatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both are known to have a substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium and conditioned the results on psychiatric disorders using GWAS summary statistics, to investigate their shared and divergent genetic architectures. Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, which remained associated after conditioning and has previously been implicated in risk-taking, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, lower socioeconomic status, pain, lower educational attainment, reproductive traits, risk-taking, sleep disturbances, and poorer overall general health. After conditioning, the genetic correlations between SA and psychiatric disorders decreased, whereas those with non-psychiatric traits remained largely unchanged. Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest the existence of a shared genetic etiology between SA and known risk factors that is not mediated by psychiatric disorders.

Subjective Sleep Debt Is Correlated with Body Fat Percentage Independent of Sleep Duration

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1675-P
Author(s):  
XIAO TAN ◽  
CHRISTIAN BENEDICT
Keyword(s):  
Sleep Duration ◽  
Body Fat ◽  
Body Fat Percentage ◽  
Fat Percentage ◽  
Subjective Sleep ◽  
Sleep Debt
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