Dataset Information

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 (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.

SUBMITTER: Mahon PB

PROVIDER: S-EPMC3665341 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Mahon Pamela Belmonte PB 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

The American journal of psychiatry 20090915 11

<h4>Objective</h4>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.<h4>Method</h4>Subjects were ascertained from two studies: the NIMH Genet ...[more]

PMID: 19755578

Similar Datasets

Project description:BackgroundThere is often a pronounced disagreement between results obtained from different genome-wide association studies in cattle. There are multiple reasons for this disagreement. Particularly the presence of false positives leads to a need to validate detected QTL before they are optimally incorporated or weighted in selection decisions or further studied for causal gene. In dairy cattle progeny testing scheme new data is routinely accumulated which can be used to validate previously discovered associations. However, the data is not an independent sample and the sample size may not be sufficient to have enough power to validate previous discoveries. Here we compared two strategies to validate previously detected QTL when new data is added from the same study population. We compare analyzing a combined dataset (COMB) including all data presently available to only analyzing a validation dataset (VAL) i.e. a new dataset not previously analyzed as an independent replication. Secondly, we confirm SNP detected in the Reference population (REF) (i.e. previously analyzed dataset consists of older bulls) in the VAL dataset.ResultsClearly the results from the combined (COMB) dataset which had nearly twice the sample size of other two subsets allowed the detection of far more significant associations than the two smaller subsets. The number of significant SNPs in REF (older bulls) was about four times higher compare to VAL (younger bulls) though both had similar sample sizes, 2,219 and 2,039 respectively. A total of 424 SNP-trait combinations on 22 chromosomes showed genome-wide significant association involving 284 unique SNPs in the COMB dataset. In the REF data set 101 associations (73 unique SNPs) and in the VAL 24 associations (18 unique SNPs) were found genome-wide significant. Sixty-eight percent of the SNPs in the REF dataset could be confirmed in the VAL dataset. Out of 469 unique SNPs showing chromosome-wide significant association with calving traits in the REF dataset 321 could be confirmed in the VAL dataset at P < 0.05.ConclusionsThe follow-up study for GWAS in cattle will depend on the aim of the study. If the aim is to discover novel QTL, analyses of the COMB dataset is recommended, while in case of identification of the causal mutation underlying a QTL, confirmation of the discovered SNPs are necessary to avoid following a false positive.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets