Sparse whole-genome sequencing identifies two loci for major depressive disorder.

Abstract:

:Major depressive disorder (MDD), one of the most frequently encountered forms of mental illness and a leading cause of disability worldwide, poses a major challenge to genetic analysis. To date, no robustly replicated genetic loci have been identified, despite analysis of more than 9,000 cases. Here, using low-coverage whole-genome sequencing of 5,303 Chinese women with recurrent MDD selected to reduce phenotypic heterogeneity, and 5,337 controls screened to exclude MDD, we identified, and subsequently replicated in an independent sample, two loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene (P = 2.53 × 10(-10)), the other in an intron of the LHPP gene (P = 6.45 × 10(-12)). Analysis of 4,509 cases with a severe subtype of MDD, melancholia, yielded an increased genetic signal at the SIRT1 locus. We attribute our success to the recruitment of relatively homogeneous cases with severe illness.

journal_name

Nature

journal_title

Nature

authors

CONVERGE consortium.

doi

10.1038/nature14659

subject

Has Abstract

pub_date

2015-07-30 00:00:00

pages

588-91

issue

7562

eissn

0028-0836

issn

1476-4687

pii

nature14659

journal_volume

523

pub_type

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