title: Applying polygenic risk scores to postpartum depression.
abstract: 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.
authors.affiliation: Queensland Brain Institute, The University of Queensland, Upland Road, St. Lucia, Brisbane, QLD, 4072, Australia, enda.byrne@uq.edu.au.
authors.forename: Enda M
authors.initials: EM
authors.lastname: Byrne
authors.forename: Tania
authors.initials: T
authors.lastname: Carrillo-Roa
authors.forename: Brenda W J H
authors.initials: BW
authors.lastname: Penninx
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Sallis
authors.forename: Alexander
authors.initials: A
authors.lastname: Viktorin
authors.forename: Brett
authors.initials: B
authors.lastname: Chapman
authors.forename: Anjali K
authors.initials: AK
authors.lastname: Henders
authors.forename: Michele L
authors.initials: ML
authors.lastname: Pergadia
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Heath
authors.forename: Pamela A F
authors.initials: PA
authors.lastname: Madden
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Sullivan
authors.forename: Lynn
authors.initials: L
authors.lastname: Boschloo
authors.forename: Gerard
authors.initials: G
authors.lastname: van Grootheest
authors.forename: George
authors.initials: G
authors.lastname: McMahon
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Lawlor
authors.forename: Mikael
authors.initials: M
authors.lastname: Landén
authors.forename: Paul
authors.initials: P
authors.lastname: Lichtenstein
authors.forename: Patrik K E
authors.initials: PK
authors.lastname: Magnusson
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Samantha
authors.initials: S
authors.lastname: Meltzer-Brody
authors.forename: Naomi R
authors.initials: NR
authors.lastname: Wray
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics; D019052:Depression, Postpartum / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D020412:Multifactorial Inheritance; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012307:Risk Factors; D011795:Surveys and Questionnaires; D055815:Young Adult