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


METHODS
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.
Mahon
Pamela Belmonte
PB
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
Payne
Jennifer L
JL
MacKinnon
Dean F
DF
Mondimore
Francis M
FM
Goes
Fernando S
FS
Schweizer
Barbara
B
Jancic
Dubravka
D
Coryell
William H
WH
Holmans
Peter A
PA
Shi
Jianxin
J
Knowles
James A
JA
Scheftner
William A
WA
Weissman
Myrna M
MM
Levinson
Douglas F
DF
DePaulo
J Raymond
JR
Zandi
Peter P
PP
Potash
James B
JB
D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D019052:Depression, Postpartum / Q000175:diagnosis* / Q000235:genetics*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D018895:Microsatellite Repeats; D008875:Middle Aged; D008957:Models, Genetic; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011247:Pregnancy