Genome-wide significant risk loci for mood disorders in the Old Order Amish founder population

Author:

Humphries Elizabeth M.,Ahn Kwangmi,Kember Rachel L.,Lopes Fabiana L.,Mocci Evelina,Peralta Juan M.,Blangero John,Glahn David C.,Goes Fernando S.,Zandi Peter P.,Kochunov Peter,Van Hout Cristopher,Shuldiner Alan R.,Pollin Toni I.,Mitchell Braxton D.,Bucan Maja,Hong L. Elliot,McMahon Francis J.,Ament Seth A.ORCID,

Abstract

ABSTRACTBackgroundGenome-wide association studies (GWAS) of mood disorders in large case-control cohorts have identified numerous risk loci, yet pathophysiological mechanisms remain elusive, primarily due to the very small effects of common variants.MethodsWe sought to discover risk variants with larger effects by conducting a genome-wide association study of mood disorders in a founder population, the Old Order Amish (OOA, n=1,672).ResultsOur analysis revealed four genome-wide significant risk loci, all of which were associated with >2-fold relative risk. Quantitative behavioral and neurocognitive assessments (n=314) revealed effects of risk variants on sub-clinical depressive symptoms and information processing speed. Network analysis suggested that OOA-specific risk loci harbor novel risk-associated genes that interact with known neuropsychiatry-associated genes via gene interaction networks. Annotation of the variants at these risk loci revealed population-enriched, non-synonymous variants in two genes encoding neurodevelopmental transcription factors, CUX1 and CNOT1.ConclusionsOur findings provide insight into the genetic architecture of mood disorders and a substrate for mechanistic and clinical studies.

Publisher

Cold Spring Harbor Laboratory

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3