Quantifying the mapping precision of genome-wide association studies using whole-genome sequencing data

Genome Biology
Yang WuJian Yang

Abstract

Understanding the mapping precision of genome-wide association studies (GWAS), that is the physical distances between the top associated single-nucleotide polymorphisms (SNPs) and the causal variants, is essential to design fine-mapping experiments for complex traits and diseases. Using simulations based on whole-genome sequencing (WGS) data from 3642 unrelated individuals of European descent, we show that the association signals at rare causal variants (minor allele frequency ≤ 0.01) are very unlikely to be mapped to common variants in GWAS using either WGS data or imputed data and vice versa. We predict that at least 80% of the common variants identified from published GWAS using imputed data are within 33.5 Kbp of the causal variants, a resolution that is comparable with that using WGS data. Mapping precision at these loci will improve with increasing sample sizes of GWAS in the future. For rare variants, the mapping precision of GWAS using WGS data is extremely high, suggesting WGS is an efficient strategy to detect and fine-map rare variants simultaneously. We further assess the mapping precision by linkage disequilibrium between GWAS hits and causal variants and develop an online tool (gwasMP) to query our results with di...Continue Reading

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Citations

Oct 26, 2018·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·V TamD Meyre
Feb 27, 2020·Nature Reviews. Genetics·Christina M Grozinger, Amro Zayed
May 28, 2020·European Journal of Human Genetics : EJHG·Chao XuHong-Wen Deng
Aug 1, 2018·Nature Genetics·Jonas B NielsenCristen J Willer
May 31, 2018·Nature Reviews. Genetics·Daniel J SchaidNicholas B Larson
Aug 21, 2020·Proceedings of the National Academy of Sciences of the United States of America·Wenran LiWing Hung Wong
Oct 7, 2020·International Journal of Molecular Sciences·Ashley HallKimberley J Billingsley
Aug 4, 2020·Human Molecular Genetics·Joshua J DibbleChris P Ponting
Sep 9, 2020·Annual Review of Genetics·Christopher M Jakobson, Daniel F Jarosz
Nov 20, 2020·Computational and Structural Biotechnology Journal·Xuanshi LiuWei Li
Sep 11, 2020·Journal of Lipid Research·David G ThomasAlan R Tall
Feb 9, 2021·Journal of Lipid Research·David G ThomasAlan R Tall
May 6, 2019·Cell Systems·Christopher M Jakobson, Daniel F Jarosz
Mar 29, 2021·Lancet Neurology·Matthew TraylorUNKNOWN International Stroke Genetics Consortium
Mar 8, 2021·G3 : Genes - Genomes - Genetics·Cory A WellerAlan O Bergland
Apr 13, 2021·Frontiers in Medicine·Atiyeh M Abdallah, Marawan Abu-Madi
Nov 6, 2021·Nature Genetics·Longda JiangJian Yang

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Methods Mentioned

BETA
genotyping

Software Mentioned

IMPUTE2
SHAPEIT
GCTA
gwasMP
GIANT
PLINK

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