AIMS:

1) To perform a genome-wide association study (GWAS) of postnatal depression (PND)

2) To investigate whether the power to detect PND is improved by incorporating information from nominally significant SNPs in a polygenic risk score

HYPOTHESIS:

1) We hypothesise that common variants contribute to the susceptibility to PND, and that a meta-analysis of GWAS studies can identify regions containing variants relating to this trait.

2) Additionally we hypothesise that our ability to predict PND will be improved by increasing the SNPs included in a genetic risk score, even if they do not achieve genome-wide significance.

VARIABLES:

The outcome variable will be PND case-control status. Women will be classified as cases or controls based on their score in the Edinburgh Postnatal Depression Scale (EPDS) measured 8 weeks postpartum. For the profile scoring, the exposure variable will be the polygenic risk score as calculated from the imputed genotype data available for mothers in ALSPAC. Association results from the Psychiatric Genetics Consortium meta-analysis of bipolar disorder (PGC-BPD) will be used to determine the SNPs to be included in the risk score. Several versions of this risk score will be computed using p-value thresholds of varying stringency (pless than 0.001, 0.01, 0.05, 0.1, 0.5, all SNPs) for inclusion in the score. Ancestry principle components will also be adjusted for.

METHODS:

Mothers enrolled in the ALSPAC cohort who have contributed genetic data to the study, and on whom we have information relating to postnatal depression at 8 weeks postpartum, will be used as the study sample.

We will perform a GWAS using the binary PND variable, and these results will be meta-analysed together those from previous GWAS studies. Polygenic risk scores will be derived using the clumped association results available from the PGC-BPD study. A number of p-value thresholds will be used to determine which of these SNPs to include in the risk score for PND.

Women will be classified as cases or controls based on their score in the Edinburgh Postnatal Depression Scale (EPDS) measured 8 weeks postpartum. A logistic regression model will be constructed, including the risk score and adjusting for both ancestry principle components and season of birth. Each version of the risk score will be incorporated into this model in turn to distinguish between PND cases and controls.

Participants will be excluded from the analysis either if they have a history of BPD or if they experienced a stillbirth or early neonatal death (within 27 days).