Applying polygenic risk scores to postpartum depression

Enda M. Byrne, Tania Carrillo-Roa, Brenda W. J. H. Penninx, Hannah M. Sallis, Alexander Viktorin, Brett Chapman, Anjali K. Henders, Psychiatric Genomic Consortium Major Depressive Disorder Working Group, Michele L. Pergadia, Andrew C. Heath, Pamela A. F. Madden, Patrick F. Sullivan, Lynn Boschloo, Gerard van Grootheest, George McMahon, Debbie A. Lawlor, Mikael Landén, Paul Lichtenstein, Patrik K. E. Magnusson, David M. Evans, Grant W. Montgomery, Dorret I. Boomsma, Nicholas G. Martin, Samantha Meltzer-Brody, Naomi R. Wray

The etiology of major depressive disorder (MDD) is likely to be heterogeneous, but postpartum depression (PPD) is hypothesized to represent a more homogenous subset of MDD. We use genome-wide SNP data to explore this hypothesis. We assembled a total cohort of 1,420 self-report cases of PPD and 9,473 controls with genome-wide genotypes from Australia, The Netherlands, Sweden and the UK. We estimated the total variance attributable to genotyped variants. We used association results from the Psychiatric Genomics Consortia (PGC) of bipolar disorder (BPD) and MDD to create polygenic scores in PPD and related MDD data sets to estimate the genetic overlap between the disorders. We estimated that the percentage of variance on the liability scale explained by common genetic variants to be 0.22 with a standard error of 0.12, p = 0.02. The proportion of variance (R (2)) from a logistic regression of PPD case/control status in all four cohorts on a SNP profile score weighted by PGC-BPD association results was small (0.1 %) but significant (p = 0.004) indicating a genetic overlap between BPD and PPD. The results were highly significant in the Australian and Dutch cohorts (R (2) > 1.1 %, p < 0.008), where the majority of cases met criteria for MDD. The genetic overlap between BPD and MDD was not significant in larger Australian and Dutch MDD case/control cohorts after excluding PPD cases (R (2) = 0.06 %, p = 0.08), despite the larger MDD group affording more power. Our results suggest an empirical genetic evidence for a more important shared genetic etiology between BPD and PPD than between BPD and MDD.