A mega-analysis of genome-wide association studies for major depressive disorder

重性抑郁障碍 全基因组关联研究 单核苷酸多态性 遗传关联 双相情感障碍 肿瘤科 遗传学 医学 精神科 生物 基因型 基因 认知
作者
Stephan Ripke,Naomi R. Wray,Cathryn M. Lewis,Steven P. Hamilton,Myrna M. Weissman,Gerome Breen,Enda M. Byrne,Douglas Blackwood,Dorret I. Boomsma,Sven Cichon,Andrew C. Heath,Herta Flor,Susanne Lucae,Pamela A. F. Madden,Nicholas G. Martin,Peter McGuffin,Pierandrea Muglia,Markus M. Nöethen,Brenda P Penninx,Michele L. Pergadia
出处
期刊:Molecular Psychiatry [Springer Nature]
卷期号:18 (4): 497-511 被引量:1116
标识
DOI:10.1038/mp.2012.21
摘要

Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 × 10(-8)), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083-53 822 102, minimum P=5.9 × 10(-9) at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
在水一方应助Nayvue采纳,获得10
刚刚
3秒前
Ryan完成签到,获得积分10
4秒前
General完成签到 ,获得积分10
4秒前
谦让汝燕完成签到,获得积分10
6秒前
wellyou完成签到,获得积分10
7秒前
mint完成签到,获得积分10
9秒前
afli完成签到 ,获得积分0
12秒前
13秒前
Yy完成签到 ,获得积分10
16秒前
Nayvue发布了新的文献求助10
18秒前
feng完成签到,获得积分10
18秒前
淡淡的小蘑菇完成签到 ,获得积分10
21秒前
G_Serron完成签到,获得积分10
22秒前
swordshine完成签到,获得积分10
22秒前
Anonymous完成签到,获得积分10
26秒前
medzhou完成签到,获得积分10
30秒前
儒雅的千秋完成签到,获得积分10
38秒前
普鲁卡因发布了新的文献求助10
41秒前
小雯完成签到,获得积分10
42秒前
搞怪梦寒完成签到,获得积分20
43秒前
喵了个咪完成签到 ,获得积分10
44秒前
mc完成签到 ,获得积分10
46秒前
量子星尘发布了新的文献求助10
49秒前
50秒前
50秒前
虚幻谷波完成签到,获得积分10
52秒前
ruochenzu发布了新的文献求助10
55秒前
小马甲应助搞怪梦寒采纳,获得10
57秒前
firewood完成签到 ,获得积分10
58秒前
天天快乐应助普鲁卡因采纳,获得10
1分钟前
orixero应助NXK采纳,获得10
1分钟前
bjr完成签到 ,获得积分10
1分钟前
研友_LwlAgn完成签到,获得积分10
1分钟前
陈昊完成签到,获得积分10
1分钟前
1分钟前
tian发布了新的文献求助10
1分钟前
1分钟前
1分钟前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038128
求助须知:如何正确求助?哪些是违规求助? 3575831
关于积分的说明 11373827
捐赠科研通 3305610
什么是DOI,文献DOI怎么找? 1819255
邀请新用户注册赠送积分活动 892655
科研通“疑难数据库(出版商)”最低求助积分说明 815022