Genome-wide linkage and follow-up association study of postpartum mood symptoms
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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 (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. 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.
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Post-birth decompensation in women with bipolar disorder is caused by genetic factors and by massive gonadal steroid withdrawal after birth in women who are neurobiologically sensitive to hormonal change.
“The causes of post-birth decompensation in women with bipolar disorder include genetic factors [31–33] and massive gonadal steroid withdrawal after birth in women who are neurobiologically sensitive to hormonal change [34].”
From Perinatal mental illness: Definition, description and aetiology (2014) · cites this paper as [32]
Genome-wide data suggest that genetic variations on specific chromosomes may increase susceptibility to postpartum mood symptoms.
“Genome-wide data suggested that genetic variations on specific chromosomes may increase susceptibility to postpartum mood symptoms.”
From Perinatal mental illness: Definition, description and aetiology (2014) · cites this paper as [32]
Genetic studies have identified specific hereditary factors in postpartum depression.
“Genetic studies have also pointed to specific hereditary factors in postpartum depression [32].”
From Perinatal mental illness: Definition, description and aetiology (2014) · cites this paper as [32]
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Self-citation
- Authors
- Mahon, P. B., Payne, J. L., MacKinnon, D. F., Mondimore, F. M., Goes, F. S., Schweizer, B., Jancic, D., NIMH Genetics Initiative Bipolar Disorder Consortium, BiGS Consortium, Coryell, W. H., Holmans, P. A., Shi, J., Knowles, J. A., Scheftner, W. A., Weissman, M. M., Levinson, D. F., DePaulo, J. R., Zandi, P. P., & Potash, J. B.
- Affiliations
- Johns Hopkins University (US)
- University of Southern California (US)
- University of Iowa (US)
- Rush University (US)
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2009-11
- Volume
- 166
- Issue
- 11
- Pages
- 1229-1237
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC3665341
- OpenAlex
- W1967585364
- Cited by
- 112
- References
- 45
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 4 · 2023: 6 · 2022: 3 · 2021: 10 · 2020: 4 · 2019: 9 · 2018: 10 · 2017: 3 · 2016: 4 · 2015: 5 · 2014: 11 · 2013: 10 · 2012: 9
- FWCI
- 8.03
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01hg065403-000, 5u01mh046280-08, 5u01mh046274-08)
- National Institute of Mental Health (MH59566, R01MH59533, R01 MH60068, R01MH59545, R01 MH59553, MH-60870, R01 MH59567, K24MH064197, R01MH059553, R01MH059541, MH-059565, R01 MH 59535, MH067257, MH-061675, R01MH60866, MH-59586, Z01MH002810, R01MH059566, 1K24MH64197, R01MH059571, MH-059571, R01MH059545, R01MH060879, R01MH059565, U01MH46282, R01MH059542, R01MH060870, R01MH059534, R01MH059533, U01 MH-060879, R01MH061675, U01MH046282, R01MH059567, R01MH059556, R01MH059586, R01 MH61686, R01MH060866, R01MH059588, R01MH059535, R01MH067257, K23MH074799, U01 MH 46280, K01MH072866, MH-59587, R01MH059548, R01MH060912, R01MH060068, R01MH059552, R01MH061686, MH-059588, R01MH059587, U01 MH 46274)
- National Human Genome Research Institute (N01 HG065403)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- postpartum depression, genetic susceptibility, genome-wide linkage analysis, single nucleotide polymorphisms, HMCN1, estrogen receptor binding sites, bipolar disorder, microsatellite markers
- MeSH terms
- Adult, Bipolar Disorder, Chromosome Mapping, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 9, Major Depressive Disorder, Female, Follow-Up Studies, Genotype, Humans, Genetic Linkage, Middle Aged, Models, Genetic, Pedigree, Pregnancy, Genetic Variation, Microsatellite Repeats, Depression, Postpartum, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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