scholarly journals The Impact of Improved Microarray Coverage and Larger Sample Sizes on Future Genome-Wide Association Studies

2013 ◽  
Vol 37 (4) ◽  
pp. 383-392 ◽  
Author(s):  
Karla J. Lindquist ◽  
Eric Jorgenson ◽  
Thomas J. Hoffmann ◽  
John S. Witte
Keyword(s):  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Sample Sizes ◽  
Genome Wide ◽  
The Impact ◽  
Larger Sample

scholarly journals Importance of SNP Dependency Correction and Association Integration for Gene Set Analysis in Genome-Wide Association Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
Michal Marczyk ◽  
Agnieszka Macioszek ◽  
Joanna Tobiasz ◽  
Joanna Polanska ◽  
Joanna Zyla
Keyword(s):  
Association Studies ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Genome Wide Association ◽  
Gene Set Analysis ◽  
Genome Wide Association Studies ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Genome Wide ◽  
The Impact

A typical genome-wide association study (GWAS) analyzes millions of single-nucleotide polymorphisms (SNPs), several of which are in a region of the same gene. To conduct gene set analysis (GSA), information from SNPs needs to be unified at the gene level. A widely used practice is to use only the most relevant SNP per gene; however, there are other methods of integration that could be applied here. Also, the problem of nonrandom association of alleles at two or more loci is often neglected. Here, we tested the impact of incorporation of different integrations and linkage disequilibrium (LD) correction on the performance of several GSA methods. Matched normal and breast cancer samples from The Cancer Genome Atlas database were used to evaluate the performance of six GSA algorithms: Coincident Extreme Ranks in Numerical Observations (CERNO), Gene Set Enrichment Analysis (GSEA), GSEA-SNP, improved GSEA for GWAS (i-GSEA4GWAS), Meta-Analysis Gene-set Enrichment of variaNT Associations (MAGENTA), and Over-Representation Analysis (ORA). Association of SNPs to phenotype was calculated using modified McNemar’s test. Results for SNPs mapped to the same gene were integrated using Fisher and Stouffer methods and compared with the minimum p-value method. Four common measures were used to quantify the performance of all combinations of methods. Results of GSA analysis on GWAS were compared to the one performed on gene expression data. Comparing all evaluation metrics across different GSA algorithms, integrations, and LD correction, we highlighted CERNO, and MAGENTA with Stouffer as the most efficient. Applying LD correction increased prioritization and specificity of enrichment outcomes for all tested algorithms. When Fisher or Stouffer were used with LD, sensitivity and reproducibility were also better. Using any integration method was beneficial in comparison with a minimum p-value method in specific combinations. The correlation between GSA results from genomic and transcriptomic level was the highest when Stouffer integration was combined with LD correction. We thoroughly evaluated different approaches to GSA in GWAS in terms of performance to guide others to select the most effective combinations. We showed that LD correction and Stouffer integration could increase the performance of enrichment analysis and encourage the usage of these techniques.

scholarly journals Fine-scale population structure in the UK Biobank: implications for genome-wide association studies

2020 ◽  
Vol 29 (16) ◽  
pp. 2803-2811
Author(s):  
James P Cook ◽  
Anubha Mahajan ◽  
Andrew P Morris
Keyword(s):  
Population Structure ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Fine Scale ◽  
Uk Biobank ◽  
Genome Wide ◽  
Scale Population ◽  
The Uk ◽  
The Impact

Abstract The UK Biobank is a prospective study of more than 500 000 participants, which has aggregated data from questionnaires, physical measures, biomarkers, imaging and follow-up for a wide range of health-related outcomes, together with genome-wide genotyping supplemented with high-density imputation. Previous studies have highlighted fine-scale population structure in the UK on a North-West to South-East cline, but the impact of unmeasured geographical confounding on genome-wide association studies (GWAS) of complex human traits in the UK Biobank has not been investigated. We considered 368 325 white British individuals from the UK Biobank and performed GWAS of their birth location. We demonstrate that widely used approaches to adjust for population structure, including principal component analysis and mixed modelling with a random effect for a genetic relationship matrix, cannot fully account for the fine-scale geographical confounding in the UK Biobank. We observe significant genetic correlation of birth location with a range of lifestyle-related traits, including body-mass index and fat mass, hypertension and lung function, even after adjustment for population structure. Variants driving associations with birth location are also strongly associated with many of these lifestyle-related traits after correction for population structure, indicating that there could be environmental factors that are confounded with geography that have not been adequately accounted for. Our findings highlight the need for caution in the interpretation of lifestyle-related trait GWAS in UK Biobank, particularly in loci demonstrating strong residual association with birth location.

The Impact of Large-Scale Genomic Methods in Orthopaedic Disorders: Insights from Genome-Wide Association Studies

2014 ◽  
Vol 96 (5) ◽  
pp. e38-1-10 ◽  
Author(s):  
Nandina Paria ◽  
Lawson A Copley ◽  
John A Herring ◽  
Harry KW Kim ◽  
B Stephens Richards ◽  
...  
Keyword(s):  
Large Scale ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
The Impact

The Impact of Removing Former Drinkers from Genome‐wide Association Studies of AUDIT‐C

Addiction ◽  
2021 ◽  
Author(s):  
Cecilia Dao ◽  
Hang Zhou ◽  
Aeron Small ◽  
Kirsha S. Gordon ◽  
Boyang Li ◽  
...  
Keyword(s):  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
The Impact

Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis: the impact of genome-wide association studies identified disease risk loci

2017 ◽  
Vol 18 (17) ◽  
pp. 1563-1574 ◽  
Author(s):  
Olga Kulakova ◽  
Vitalina Bashinskaya ◽  
Ivan Kiselev ◽  
Natalia Baulina ◽  
Ekaterina Tsareva ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Disease Risk ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
The Impact
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