A Meta-Analysis of the Genome-Wide Association Studies on Two Genetically Correlated Phenotypes Suggests Four New Risk Loci for Headaches  

作　　者：Weihua Meng Parminder S.Reel Charvi Nangia Aravind Lathika Rajendrakumar Harry L.Hebert Qian Guo Mark J.Adams Hua Zheng Zen Haut Lu Me Research Team Debashree Ray Lesley A.Colvin Colin N.A.Palmer Andrew M.McIntosh Blair H.Smith 

机构地区：[1]Nottingham Ningbo China Beacons of Excellence Research and Innovation Institute,University of Nottingham Ningbo China,Ningbo 315100,China [2]Division of Population Health and Genomics,Ninewells Hospital and Medical School,University of Dundee,Dundee DD24BF,UK [3]Division of Psychiatry,Edinburgh Medical School,University of Edinburgh,Edinburgh EH105HF,UK [4]Department of Anaesthesiology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China [5]PAPRSB Institute of Health Sciences,Universiti Brunei Darussalam,Bandar Seri Begawan BE1410,Brunei Darussalam [6]andMe,Inc.,Sunnyvale,CA 94086,USA [7]Department of Epidemiology,Bloomberg School of Public Health,Johns Hopkins University,Baltimore,MD 21205,USA [8]Department of Biostatistics,Bloomberg School of Public Health,Johns Hopkins University,Baltimore,MD 21205,USA

出　　处：《Phenomics》2023年第1期64-76,共13页表型组学（英文）

基　　金：Funding This study was mainly funded by the Wellcome Trust Strategic Award“Stratifying Resilience and Depression Longitudinally”(STRADL)with Reference Number 104036/Z/14/Z.

摘　　要：Headache is one of the commonest complaints that doctors need to address in clinical settings.The genetic mechanisms of different types of headache are not well understood while it has been suggested that self-reported headache and self-reported migraine were genetically correlated.In this study,we performed a meta-analysis of genome-wide association studies(GWAS)on the self-reported headache phenotype from the UK Biobank and the self-reported migraine phenotype from the 23andMe using the Unified Score-based Association Test(metaUSAT)software for genetically correlated phenotypes(N=397,385).We identified 38 loci for headaches,of which 34 loci have been reported before and four loci were newly suggested.The LDL receptor related protein 1(LRP1)-Signal Transducer and Activator of Transcription 6(STAT6)-Short chain Dehydrogenase/Reductase family 9C member 7(SDR9C7)region in chromosome 12 was the most significantly associated locus with a leading p value of 1.24×10^(-62)of rs11172113.The One Cut homeobox 2(ONECUT2)gene locus in chromosome 18 was the strongest signal among the four new loci with a p value of 1.29×10^(-9)of rs673939.Our study demonstrated that the genetically correlated phenotypes of self-reported headache and self-reported migraine can be meta-analysed together in theory and in practice to boost study power to identify more variants for headaches.This study has paved way for a large GWAS meta-analysis involving cohorts of different while genetically correlated headache phenotypes.

关 键 词：Headache MIGRAINE Unified Score-based Association Test Correlated phenotypes META-ANALYSIS Genome-wide association study 

分 类 号：Q78[生物学—分子生物学]