Genome-Wide Association Study of the Metabolic Syndrome in UK Biobank

AbstractTinnitus is a prevalent condition in which perception of sound occurs without an external stimulus. It is often associated with pre-existing hearing loss or noise-induced damage to the auditory system. In some individuals it occurs frequently or even continuously and leads to considerable distress and difficulty sleeping. There is little knowledge of the molecular mechanisms involved in tinnitus which has hindered the development of treatments. Evidence suggests that tinnitus has a heritable component although previous genetic studies have not established specific risk factors. From a total of 172,608 UK Biobank participants who answered questions on tinnitus we performed a case–control genome-wide association study for self-reported tinnitus. Final sample size used in association analysis was N = 91,424. Three variants in close proximity to the RCOR1 gene reached genome wide significance: rs4906228 (p = 1.7E−08), rs4900545 (p = 1.8E−08) and 14:103042287_CT_C (p = 3.50E−08). RCOR1 encodes REST Corepressor 1, a component of a co-repressor complex involved in repressing neuronal gene expression in non-neuronal cells. Eleven other independent genetic loci reached a suggestive significance threshold of p < 1E−06.

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Genome-Wide Association Study (GWAS) on Metabolic Syndrome in Subjects with Abdominal Obesity in a Taiwanese Population.

2020 IEEE International Conference on Bioinformatics and Biomedicine (BIBM) ◽

10.1109/bibm49941.2020.9313373 ◽

2020 ◽

Author(s):

Kuan-Hung Yeh ◽

Ching-Heng Lin ◽

Tzu-Hung Hsiao ◽

Tzu-Pin Lu

Keyword(s):

Metabolic Syndrome ◽

Association Study ◽

Abdominal Obesity ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Taiwanese Population ◽

Genome Wide

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Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank

PLoS Genetics ◽

10.1371/journal.pgen.1009428 ◽

2021 ◽

Vol 17 (4) ◽

pp. e1009428

Author(s):

Keira J. A. Johnston ◽

Joey Ward ◽

Pradipta R. Ray ◽

Mark J. Adams ◽

Andrew M. McIntosh ◽

...

Keyword(s):

Chronic Pain ◽

Sex Differences ◽

Association Study ◽

Genome Wide Association Study ◽

Chronic Widespread Pain ◽

Genome Wide Association ◽

System Component ◽

Widespread Pain ◽

Uk Biobank ◽

Genome Wide

Chronic pain is highly prevalent worldwide and imparts a significant socioeconomic and public health burden. Factors influencing susceptibility to, and mechanisms of, chronic pain development, are not fully understood, but sex is thought to play a significant role, and chronic pain is more prevalent in women than in men. To investigate sex differences in chronic pain, we carried out a sex-stratified genome-wide association study of Multisite Chronic Pain (MCP), a derived chronic pain phenotype, in UK Biobank on 178,556 men and 209,093 women, as well as investigating sex-specific genetic correlations with a range of psychiatric, autoimmune and anthropometric phenotypes and the relationship between sex-specific polygenic risk scores for MCP and chronic widespread pain. We also assessed whether MCP-associated genes showed expression pattern enrichment across tissues. A total of 123 SNPs at five independent loci were significantly associated with MCP in men. In women, a total of 286 genome-wide significant SNPs at ten independent loci were discovered. Meta-analysis of sex-stratified GWAS outputs revealed a further 87 independent associated SNPs. Gene-level analyses revealed sex-specific MCP associations, with 31 genes significantly associated in females, 37 genes associated in males, and a single gene, DCC, associated in both sexes. We found evidence for sex-specific pleiotropy and risk for MCP was found to be associated with chronic widespread pain in a sex-differential manner. Male and female MCP were highly genetically correlated, but at an rg of significantly less than 1 (0.92). All 37 male MCP-associated genes and all but one of 31 female MCP-associated genes were found to be expressed in the dorsal root ganglion, and there was a degree of enrichment for expression in sex-specific tissues. Overall, the findings indicate that sex differences in chronic pain exist at the SNP, gene and transcript abundance level, and highlight possible sex-specific pleiotropy for MCP. Results support the proposition of a strong central nervous-system component to chronic pain in both sexes, additionally highlighting a potential role for the DRG and nociception.

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Genome-Wide Association Meta-Analysis Supports Genes Involved in Valve and Cardiac Development to Associate With Mitral Valve Prolapse

Circulation Genomic and Precision Medicine ◽

10.1161/circgen.120.003148 ◽

2021 ◽

Author(s):

Mengyao Yu ◽

Sergiy Kyryachenko ◽

Stephanie Debette ◽

Philippe Amouyel ◽

Jean-Jacques Schott ◽

...

Keyword(s):

Mitral Valve ◽

Association Study ◽

Genome Wide Association Study ◽

Cardiac Development ◽

Meta Analysis ◽

Genome Wide Association ◽

Uk Biobank ◽

Additional Risk ◽

Genome Wide ◽

The Uk

Background: Mitral valve prolapse (MVP) is a common cardiac valve disease, which affects 1 in 40 in the general population. Previous genome-wide association study have identified 6 risk loci for MVP. But these loci explained only partially the genetic risk for MVP. We aim to identify additional risk loci for MVP by adding data set from the UK Biobank. Methods: We reanalyzed 1007/479 cases from the MVP-France study, 1469/862 controls from the MVP-Nantes study for reimputation genotypes using HRC and TOPMed panels. We also incorporated 434 MVP cases and 4527 controls from the UK Biobank for discovery analyses. Genetic association was conducted using SNPTEST and meta-analyses using METAL. We used FUMA for post-genome-wide association study annotations and MAGMA for gene-based and gene-set analyses. Results: We found TOPMed imputation to perform better in terms of accuracy in the lower ranges of minor allele frequency below 0.1. Our updated meta-analysis included UK Biobank study for ≈8 million common single-nucleotide polymorphisms (minor allele frequency >0.01) and replicated the association on Chr2 as the top association signal near TNS1 . We identified an additional risk locus on Chr1 ( SYT2 ) and 2 suggestive risk loci on chr8 ( MSRA ) and chr19 ( FBXO46 ), all driven by common variants. Gene-based association using MAGMA revealed 6 risk genes for MVP with pronounced expression levels in cardiovascular tissues, especially the heart and globally part of enriched GO terms related to cardiac development. Conclusions: We report an updated meta-analysis genome-wide association study for MVP using dense imputation coverage and an improved case-control sample. We describe several loci and genes with MVP spanning biological mechanisms highly relevant to MVP, especially during valve and heart development.

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Genome-Wide Association Study of Metabolic Syndrome Reveals Primary Genetic Variants at CETP Locus in Indians

Biomolecules ◽

10.3390/biom9080321 ◽

2019 ◽

Vol 9 (8) ◽

pp. 321 ◽

Cited By ~ 3

Author(s):

Gauri Prasad ◽

Khushdeep Bandesh ◽

Anil Giri ◽

Yasmeen Kauser ◽

Prakriti Chanda ◽

...

Keyword(s):

Metabolic Syndrome ◽

Adipose Tissue ◽

Association Study ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Rapid Urbanization ◽

Significance Level ◽

Genome Wide ◽

A Genome ◽

Replication Phase

Indians, a rapidly growing population, constitute vast genetic heterogeneity to that of Western population; however they have become a sedentary population in past decades due to rapid urbanization ensuing in the amplified prevalence of metabolic syndrome (MetS). We performed a genome-wide association study (GWAS) of MetS in 10,093 Indian individuals (6617 MetS and 3476 controls) of Indo-European origin, that belong to our previous biorepository of The Indian Diabetes Consortium (INDICO). The study was conducted in two stages—discovery phase (N = 2158) and replication phase (N = 7935). We discovered two variants within/near the CETP gene—rs1800775 and rs3816117—associated with MetS at genome-wide significance level during replication phase in Indians. Additional CETP loci rs7205804, rs1532624, rs3764261, rs247617, and rs173539 also cropped up as modest signals in Indians. Haplotype association analysis revealed GCCCAGC as the strongest haplotype within the CETP locus constituting all seven CETP signals. In combined analysis, we perceived a novel and functionally relevant sub-GWAS significant locus—rs16890462 in the vicinity of SFRP1 gene. Overlaying gene regulatory data from ENCODE database revealed that single nucleotide polymorphism (SNP) rs16890462 resides in repressive chromatin in human subcutaneous adipose tissue as characterized by the enrichment of H3K27me3 and CTCF marks (repressive gene marks) and diminished H3K36me3 marks (activation gene marks). The variant displayed active DNA methylation marks in adipose tissue, suggesting its likely regulatory activity. Further, the variant also disrupts a potential binding site of a key transcription factor, NRF2, which is known for involvement in obesity and metabolic syndrome.

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