Weissman MM, Knowles JK, Zubenko GS, Zubenko WN, DePaulo JR, McInnis MG, MacKinnon D, Levinson DF, Gladis MM, Murphy-Eberenz K, Holmans P, Crowe RR, Coryell WH, Scheftner WA, Nurnberger J, Miller M, Bowman E, Reich T, Goate A, Rice J, DePaulo JR Jr, Simpson S, Stine C, Gershon E, Kazuba D, Maxwell E, Nurnberger J, Miller MJ, Bowman ES, Rau NL, Moe PR, Samavedy N, El-Mallakh R, Manji H, Glitz DA, Meyer ET, Smiley C, Foroud T, Flury L, Dick DM, Edenberg H, Rice J, Reich T, Goate A, Bierut L, McInnis M, DePaulo JR Jr, MacKinnon DF, Mondimore FM, Potash JB, Zandi PP, Avramopoulos D, Payne J, Berrettini W, Byerley W, Vawter M, Coryell W, Crowe R, Gershon E, Badner J, McMahon F, Liu C, Sanders A, Caserta M, Dinwiddie S, Nguyen T, Harakal D, Kelsoe J, McKinney R, Scheftner W, Kravitz HM, Marta D, Vaughn-Brown A, Bederow L, McMahon FJ, Kassem L, Detera-Wadleigh S, Austin L, Murphy DL, Gejman PV, Sanders AR, Amin F, Buccola N, Byerley W, Cloninger CR, Crowe R, Black D, Freedman R, Levinson D, Mowry B, Silverman J, Kelsoe JR, Greenwood TA, Nievergelt C, Schork N, Smith EN, Bloss C, Nurnberger J, Edenberg HJ, Foroud T, Gershon E, Liu C, Badner JA, Scheftner WA, Lawson WB, Nwulia EA, Hipolito M, Coryell W, Rice J, Byerley W, McMahon F, Schulze TG, Berrettini W, Potash JB, Zandi PP, Mahon PB, McInnis MG, Zöllner S, Craig D, Szelinger S.
Source
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
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 (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.