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一项针对两种遗传相关表型的全基因组关联研究的荟萃分析表明存在四个新的头痛风险基因座。

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

作者信息

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

机构信息

Nottingham Ningbo China Beacons of Excellence Research and Innovation Institute, University of Nottingham Ningbo China, Ningbo, 315100 China.

Division of Population Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD2 4BF UK.

出版信息

Phenomics. 2022 Nov 18;3(1):64-76. doi: 10.1007/s43657-022-00078-7. eCollection 2023 Feb.

Abstract

UNLABELLED

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 ( = 397,385). We identified 38 loci for headaches, of which 34 loci have been reported before and four loci were newly suggested. The  ()- ()- / () region in chromosome 12 was the most significantly associated locus with a leading value of 1.24 × 10 of rs11172113. The () gene locus in chromosome 18 was the strongest signal among the four new loci with a value of 1.29 × 10 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.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s43657-022-00078-7.

摘要

未标注

头痛是医生在临床环境中需要处理的最常见病症之一。虽然有研究表明自我报告的头痛和自我报告的偏头痛存在遗传相关性,但不同类型头痛的遗传机制尚未得到充分理解。在本研究中,我们使用基于统一分数的关联检验(metaUSAT)软件,对来自英国生物银行的自我报告头痛表型和来自23andMe的自我报告偏头痛表型进行了全基因组关联研究(GWAS)的荟萃分析(样本量=397,385)。我们确定了38个头痛相关位点,其中34个位点之前已有报道,4个位点为新发现。12号染色体上的()-()- / ()区域是最显著相关的位点,rs11172113的领先值为1.24×10。18号染色体上的()基因位点是四个新位点中最强的信号,rs673939的 值为1.29×10。我们的研究表明,自我报告头痛和自我报告偏头痛的遗传相关表型在理论和实践中都可以一起进行荟萃分析,以提高识别更多头痛相关变异的研究能力。这项研究为涉及不同但遗传相关头痛表型队列的大型GWAS荟萃分析铺平了道路。

补充信息

在线版本包含可在10.1007/s43657-022-00078-7获取的补充材料。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abc0/9883370/5350c29c4396/43657_2022_78_Fig1_HTML.jpg

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