Genome-Wide Linkage and Follow-Up Association Study of Postpartum Mood Symptoms

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.

Understanding Bipolar Disorder: The Epigenetic Perspective

“…There are many reports showing frequent occurrence of maternal transmission of BPD in familial cases (Kato et al 1996;Kornberg et al 2000;Lambert and Gill 2002;Lan et al 2007;Stine et al 1995). This observation has led investigators to hypothesize involvement of the X chromosome, however, several linkage studies failed to detect major genetic factors on the X chromosome and therefore failed to explain parentof-origin effects in mood disorders, including BPD (Gershon and Bunney 1977;Hamshere et al 2009;Mahon et al 2009;Palo et al 2010). Other modes of inheritance that might explain parent-of-origin effects are mitochondrial inheritance and genomic imprinting.…”

Employment During Pregnancy Protects Against Postpartum Depression

“…While different biological (Albacar et al, 2011;Brummelte & Galea, 2010;Leung & Kaplan, 2009) and genetic (Costas et al, 2010;Mahon et al, 2009;Sanjuan et al, 2008;Treloar, Martin, Bucholz, Madden, & Heath, 1999) factors have been associated with PPD, most researchers have identified a history of affective disorder, depressive episodes and anxiety during pregnancy as the principal risk factors for PPD (O'Hara, 2009;Oppo et al, 2009). Social and psychological factors such as marital discord, low social support, stressful life events and lack of marital support have been strongly associated with PPD in several studies (Beck, 2001;Chen, 2001;O'Hara, 2009), and unemployment, which has been associated with depression in the general population (Stankunas, Kalediene, Starkuviene, & Kapustinskiene, 2006), has been specifically associated with PPD (Chen, 2001;Inandi et al, 2002;Jardri et al, 2006;Lane et al, 1997;Miyake, Tanaka, Sasaki, & Hirota, 2011;Posmontier, 2008;Rubertsson, Wickberg, Gustavsson, & Radestad, 2005;Warner, Appleby, Whitton, & Faragher, 1996).…”

HMNC1 gene polymorphism associated with postpartum depression

“…The first genome-wide study of PPD was recently published, and showed that the hemicentin-1 (HMNC1) gene had the strongest association with postpartum mood symptoms. 2 This gene encodes an extracellular protein that contains four estrogen receptorbinding sites and is involved mainly in cell migration, protein anchorage, and the formation of hemidesmosomes in the epidermis. 3 In view of this finding, we genotyped the rs2891230 single-nucleotide polymorphism (TaqManH SNP genotyping assay, Applied Biosystems Inc, Foster City, CA, USA) of the HMCN1 gene using a 7500 Real-Time PCR System (Applied Biosystems Inc, Foster City, CA, USA), in allelic discrimination mode.…”