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

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单位: [1]Univ Nottingham Ningbo China, Nottingham Ningbo China Beacons Excellence Res & I, Ningbo 315100, Peoples R China [2]Univ Dundee, Ninewells Hosp, Div Populat Hlth & Genom, Dundee DD2, Scotland [3]Univ Dundee, Med Sch, Dundee DD2 4BF, Scotland [4]Univ Edinburgh, Edinburgh Med Sch, Div Psychiat, Edinburgh EH10 5HF, Scotland [5]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Anaesthesiol, Wuhan 430030, Peoples R China [6]Univ Brunei Darussalam, PAPRSB Inst Hlth Sci, BE-1410 Bandar Seri Begawan, Brunei [7]23andMe Inc, Sunnyvale, CA 94086 USA [8]Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA [9]Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA
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关键词: Headache Migraine Unified Score-based Association Test Correlated phenotypes Meta-analysis Genome-wide association study

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 chainDehydrogenase/Reductase family 9C member 7 (SDR9C7) region in chromosome 12 was the most significantly associated locus with a leading p value of 1.24 x 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 x 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.

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大类 | 2 区 生物学
小类 | 2 区 遗传学
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Q2 GENETICS & HEREDITY

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第一作者单位: [1]Univ Nottingham Ningbo China, Nottingham Ningbo China Beacons Excellence Res & I, Ningbo 315100, Peoples R China [2]Univ Dundee, Ninewells Hosp, Div Populat Hlth & Genom, Dundee DD2, Scotland [3]Univ Dundee, Med Sch, Dundee DD2 4BF, Scotland
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通讯机构: [1]Univ Nottingham Ningbo China, Nottingham Ningbo China Beacons Excellence Res & I, Ningbo 315100, Peoples R China [2]Univ Dundee, Ninewells Hosp, Div Populat Hlth & Genom, Dundee DD2, Scotland [3]Univ Dundee, Med Sch, Dundee DD2 4BF, Scotland
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