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

Department of Psychiatry, Columbia University, New York, New York, United States
American Journal of Psychiatry (Impact Factor: 12.3). 09/2009; 166(11):1229-37. DOI: 10.1176/appi.ajp.2009.09030417
Source: PubMed


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.
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.
The maximum linkage peak for postpartum symptoms occurred on chromosome 1q21.3-q32.1, with a chromosome-wide significant likelihood ratio Z score (Z(LR)) of 2.93 (permutation p=0.02). This was a significant increase over the baseline Z(LR) 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 (Z(LR)=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.
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.

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Available from: J Raymond Depaulo, Dec 27, 2013
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    • "There are simply too many uncontrolled variables associated with such overdetermined processes, and these clearly include many social and situational factors. Caspi and others cited earlier have further elaborated genetic environmental interactions in the determination of other complex behavioral outcomes, including personality types in adulthood, IQ, depression, psychosis, post-partum mood symptoms, and personality (Caspi et al., 2005; Hicks, South, DiRago, Iacono, & McGue, 2009; Legrand, Keyes, McGue, Iacono, & Krueger, 2008; Mahon et al., 2009; Turkheimer et al., 2003). In the end it is important not to lose sight of the importance of considering all levels of analysis in assessing individual and group risk factors. "
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    • "However, gene expression profiling revealed that FEAT also affects various cell signalling and metabolic pathways (Fig. 6b and 6c; Supplementary Table 2). Furthermore, in a recent genome-wide linkage analysis, genetic variations in the human METTL13 gene have been associated with increased susceptibility to postpartum mood syndrome 54. CpG-island microarray analyses of frontal cortex tissues have revealed higher DNA methylation close to the METTL13 gene among bipolar disorder females and psychosis females 55. "
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    • "To this end, future studies will surely include genome-wide association studies, wherein the genome of thousands of women can be compared with respect to the presence or absence of PPD, as well as continued research to evaluate the prevalence of specific candidate gene polymorphisms in women with PPD compared to those without. In fact, one such study very recently has been published (Mahon et al., 2009) wherein genome-wide techniques were used to search for genotypes that associated with any retrospectively reported postpartum mood symptoms. The data suggested a linkage between recalled postpartum mood symptoms and genes on chromosomes 1 and 9. "
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    ABSTRACT: Postpartum depression (PPD) is a serious mood disorder that may carry life-long consequences for a woman and her family. Multiple risk factors for PPD have been identified, including psychosocial, situational, and biological stimuli, several of which are experienced by most, if not all, postpartum women. Given the commonality of these risk factors, it is unclear why fewer than 20% of postpartum women actually develop PPD. In this review, we suggest that different susceptibility to PPD among postpartum women may be explained by the presence or absence of genetic variants that confer increased risk. We review three categories of genes known to code for proteins associated with depression in the general population or proteins known to be affected by childbirth for their possible association with PPD, including genes related to central nervous system monoamine availability, proinflammatory cytokines, and brain neuropeptides. Only two studies are available in the literature to date specifically looking at polymorphisms in postpartum women as related to PPD; both are concerned with monoamine availability. These are discussed in further depth. Conclusions regarding the contribution of genetic polymorphisms to the development of PPD are mixed. Ultimately, the complexity of the disorder and the interrelationships among different genes thought to contribute to depression suggest that much more research is required to understand the heritability of PPD. The complexity of the disorder also suggests that epigenetic influences must be considered as well when discussing susceptibility.
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