全基因组关联研究
表达数量性状基因座
生物
表型
遗传关联
遗传学
单核苷酸多态性
连锁不平衡
数量性状位点
大脑大小
双相情感障碍
基因
基因型
神经科学
医学
磁共振成像
放射科
认知
作者
Meng-Yuan Shang,Chuyi Zhang,Yong Wu,Lu Wang,Chuang Wang,Ming Li
出处
期刊:Cerebral Cortex
[Oxford University Press]
日期:2023-02-02
卷期号:33 (11): 6990-7000
被引量:1
标识
DOI:10.1093/cercor/bhad014
摘要
Abstract Patients with bipolar disorder (BD) and their first-degree relatives exhibit alterations in brain volume and cortical structure, whereas the underlying genetic mechanisms remain unclear. In this study, based on the published genome-wide association studies (GWAS), the extent of polygenic overlap between BD and 15 brain structural phenotypes was investigated using linkage disequilibrium score regression and MiXeR tool, and the shared genomic loci were discovered by conjunctional false discovery rate (conjFDR) and expression quantitative trait loci (eQTL) analyses. MiXeR estimated the overall measure of polygenic overlap between BD and brain structural phenotypes as 4–53% on a 0–100% scale (as quantified by the Dice coefficient). Subsequent conjFDR analyses identified 54 independent loci (71 risk single-nucleotide polymorphisms) jointly associated with BD and brain structural phenotypes with a conjFDR < 0.05, among which 33 were novel that had not been reported in the previous BD GWAS. Follow-up eQTL analyses in respective brain regions both confirmed well-known risk genes (e.g. CACNA1C, NEK4, GNL3, MAPK3) and discovered novel risk genes (e.g. LIMK2 and CAMK2N2). This study indicates a substantial shared genetic basis between BD and brain structural phenotypes, and provides novel insights into the developmental origin of BD and related biological mechanisms.
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