scholarly journals A resource-efficient tool for mixed model association analysis of large-scale data

2019 ◽  
Author(s):  
Longda Jiang ◽  
Zhili Zheng ◽  
Ting Qi ◽  
Kathryn E. Kemper ◽  
Naomi R. Wray ◽  
...  
Keyword(s):  
Population Stratification ◽  
Large Scale ◽  
Mixed Model ◽  
Genome Wide Association Study ◽  
Mixed Linear Model ◽  
Genome Wide Association ◽  
Relationship Matrix ◽  
Genome Wide ◽  
The Uk ◽  
Scale Data

ABSTRACTThe genome-wide association study (GWAS) has been widely used as an experimental design to detect associations between genetic variants and a phenotype. Two major confounding factors, population stratification and relatedness, could potentially lead to inflated GWAS test-statistics and thereby spurious associations. Mixed linear model (MLM)-based approaches can be used to account for sample structure. However, genome-wide association (GWA) analyses in biobank samples such as the UK Biobank (UKB) often exceed the capability of most existing MLM-based tools especially if the number of traits is large. Here, we developed an MLM-based tool (called fastGWA) that controls for population stratification by principal components and relatedness by a sparse genetic relationship matrix for GWA analyses of biobank-scale data. We demonstrated by extensive simulations that fastGWA is reliable, robust and highly resource-efficient. We then applied fastGWA to 2,173 traits on 456,422 array-genotyped and imputed individuals and 2,048 traits on 46,191 whole-exome-sequenced individuals in the UKB.

scholarly journals Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study

PLoS ONE ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. e0167742 ◽  
Author(s):  
Paul S. de Vries ◽  
Maria Sabater-Lleal ◽  
Daniel I. Chasman ◽  
Stella Trompet ◽  
Tarunveer S. Ahluwalia ◽  
...  
Keyword(s):  
Association Study ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
1000 Genomes ◽  
Genome Wide

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

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.

scholarly journals Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases

2020 ◽  
Vol 52 (7) ◽  
pp. 669-679 ◽  
Author(s):  
Kazuyoshi Ishigaki ◽  
Masato Akiyama ◽  
Masahiro Kanai ◽  
Atsushi Takahashi ◽  
Eiryo Kawakami ◽  
...  
Keyword(s):  
Association Study ◽  
Japanese Population ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Susceptibility Loci ◽  
Genome Wide
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