Genome-wide linkage and follow-up association study of postpartum mood symptoms

NIMH Bipolar Disorder Genetics Initiative, the "Molecular Genetics of Schizophrenia II" (MGS-2) collaboration, Bipolar Genetics Studies (BiGS) Collaboration, NIMH Genetics of Recurrent Early-Onset Depression (GenRED) project

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Abstract

Objective - Family studies have suggested that postpartum mood symptoms might have a partly genetic etiology. The authors used a genome-wide linkage analysis to search for chromosomal regions that harbor genetic variants conferring susceptibility for such symptoms. The authors then fine-mapped their best linkage regions, assessing single nucleotide polymorphisms (SNPs) for genetic association with postpartum symptoms. Method - Subjects were ascertained from two studies: the NIMH Genetics Initiative Bipolar Disorder project and the Genetics of Recurrent Early-Onset Depression. Subjects included women with a history of pregnancy, any mood disorder, and information about postpartum symptoms. In the linkage study, 1,210 women met criteria (23% with postpartum symptoms), and 417 microsatellite markers were analyzed in multipoint allele sharing analyses. For the association study, 759 women met criteria (25% with postpartum symptoms), and 16,916 SNPs in the regions of the best linkage peaks were assessed for association with postpartum symptoms. Results - The maximum linkage peak for postpartum symptoms occurred on chromosome 1q21.3-q32.1, with a chromosome-wide significant likelihood ratio Z score (ZLR) of 2.93 (permutation p=0.02). This was a significant increase over the baseline ZLR of 0.32 observed at this locus among all women with a mood disorder (permutation p=0.004). Suggestive linkage was also found on 9p24.3-p22.3 (ZLR=2.91). In the fine-mapping study, the strongest implicated gene was HMCN1 (nominal p=0.00017), containing four estrogen receptor binding sites, although this was not region-wide significant. Conclusions - This is the first study to examine the genetic etiology of postpartum mood symptoms using genome-wide data. The results suggest that genetic variations on chromosomes 1q21.3-q32.1 and 9p24.3-p22.3 may increase susceptibility to postpartum mood symptoms.

Original languageEnglish (US)
Pages (from-to)1229-1237
Number of pages9
JournalAmerican Journal of Psychiatry
Volume166
Issue number11
DOIs
StatePublished - Nov 1 2009

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ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

NIMH Bipolar Disorder Genetics Initiative, the "Molecular Genetics of Schizophrenia II" (MGS-2) collaboration, Bipolar Genetics Studies (BiGS) Collaboration, & NIMH Genetics of Recurrent Early-Onset Depression (GenRED) project (2009). Genome-wide linkage and follow-up association study of postpartum mood symptoms. American Journal of Psychiatry, 166(11), 1229-1237. https://doi.org/10.1176/appi.ajp.2009.09030417