大规模人群研究发现与脑容量相关的基因
2019-11-02 23:46
美国北卡罗来纳大学教堂山分校Hongtu Zhu等研究人员利用19629名个体的全基因组关联分析确定了影响大脑容量的变异，并利用认知和心理健康特征完善了其遗传结构。相关论文在线发表于11月1日的《自然—遗传学》。
研究人员使用包括19629名参与者的英国生物银行样本，对101种脑容量表型进行了全基因组关联研究（GWAS）。GWAS鉴定了365个独立遗传变体（显著性阈值超过4.9×10−10），并对多种表型进行了相应调整。一项基于基因的关联研究发现了157个相关基因（124个新基因），而功能基因图谱分析将146个其他基因联系在一起。先前发现的许多遗传变异和基因都与认知和心理健康特征有关。通过全基因组多基因风险评分预测，英国生物银行GWAS结果可以解释其他四项独立研究中超过6％的表型变异（P =3.13×10-24）。
总之，这项研究在变体、基因座和基因水平上鉴定了许多新的遗传关联，并加深了我们对大脑体积和其他特征之间的多效性和遗传共构关系的理解。
据了解，人脑的体积变化是可遗传的，并且与许多与脑有关的复杂性状有关。
附：英文原文
Title:Genome-wide association analysis of 19,629 individuals identifies variants influencing regional brain volumes and refines their genetic co-architecture with cognitive and mental health traits
Author:Bingxin Zhao, Tianyou Luo, Tengfei Li, Yun Li, Jingwen Zhang, Yue Shan, Xifeng Wang, Liuqing Yang, Fan Zhou & Ziliang Zhu Alzheimer’s Disease Neuroimaging Initiative, Pediatric Imaging, Neurocognition and Genetics & Hongtu Zhu
Issue&Volume:01 November 2019
Abstract: Volumetric variations of the human brain are heritable and are associated with many brain-related complex traits. Here we performed genome-wide association studies (GWAS) of 101 brain volumetric phenotypes using the UK Biobank sample including 19,629 participants. GWAS identified 365 independent genetic variants exceeding a significance threshold of 4.9 × 10−10, adjusted for testing multiple phenotypes. A gene-based association study found 157 associated genes (124 new), and functional gene mapping analysis linked 146 additional genes. Many of the discovered genetic variants and genes have previously been implicated in cognitive and mental health traits. Through genome-wide polygenic-risk-score prediction, more than 6% of the phenotypic variance (P = 3.13 × 10−24) in four other independent studies could be explained by the UK Biobank GWAS results. In conclusion, our study identifies many new genetic associations at the variant, locus and gene levels and advances our understanding of the pleiotropy and genetic co-architecture between brain volumes and other traits.
DOI:10.1038/s41588-019-0516-6
Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex
本期文章：《自然—遗传学》：Online/在线发表
