Duplication of the SLIT3 Locus on 5q35.1 Predisposes to Major Depressive Disorder

被引：48

作者：

Glessner, Joseph T. ^{[1
]}

Wang, Kai ^{[1
]}

Sleiman, Patrick M. A. ^{[1
]}

Zhang, Haitao ^{[1
]}

Kim, Cecilia E. ^{[1
]}

Flory, James H. ^{[1
]}

Bradfield, Jonathan P. ^{[1
]}

Imielinski, Marcin ^{[1
]}

Frackelton, Edward C. ^{[1
]}

Qiu, Haijun ^{[1
]}

Mentch, Frank ^{[1
]}

Grant, Struan F. A. ^{[1
,2
,3
]}

Hakonarson, Hakon ^{[1
,2
,3
]}

机构：

[1] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA

[2] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Genet, Philadelphia, PA 19104 USA

[3] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA

来源：

PLOS ONE | 2010年 / 5卷 / 12期

关键词：

GENOME-WIDE ASSOCIATION;

D O I：

10.1371/journal.pone.0015463

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Major depressive disorder (MDD) is a common psychiatric and behavioral disorder. To discover novel variants conferring risk to MDD, we conducted a whole-genome scan of copy number variation (CNV), including 1,693 MDD cases and 4,506 controls genotyped on the Perlegen 600K platform. The most significant locus was observed on 5q35.1, harboring the SLIT3 gene (P = 2x10(-3)). Extending the controls with 30,000 subjects typed on the Illumina 550 k array, we found the CNV to remain exclusive to MDD cases (P = 3.2x10(-9)). Duplication was observed in 5 unrelated MDD cases encompassing 646 kb with highly similar breakpoints. SLIT3 is integral to repulsive axon guidance based on binding to Roundabout receptors. Duplication of 5q35.1 is a highly penetrant variation accounting for 0.7% of the subset of 647 cases harboring large CNVs, using a threshold of a minimum of 10 SNPs and 100 kb. This study leverages a large dataset of MDD cases and controls for the analysis of CNVs with matched platform and ethnicity. SLIT3 duplication is a novel association which explains a definitive proportion of the largely unknown etiology of MDD.

引用

页数：9

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