Applying polygenic risk scores to postpartum depression

Psychiatric Genomic Consortium Major Depressive Disorder Working Group

Research output: Contribution to JournalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)519-528
Number of pages10
JournalArchives of womens mental health
Volume17
Issue number6
Early online date19 Jul 2014
DOIs
Publication statusPublished - Dec 2014

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Postpartum Depression
Major Depressive Disorder
Bipolar Disorder
Genomics
Single Nucleotide Polymorphism
Psychiatry
Genome
Sweden
Netherlands
Self Report
Logistic Models
Genotype

Keywords

  • Adult
  • Bipolar Disorder/genetics
  • Depression, Postpartum/genetics
  • Depressive Disorder, Major/genetics
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genotype
  • Humans
  • Logistic Models
  • Male
  • Multifactorial Inheritance
  • Polymorphism, Single Nucleotide
  • Retrospective Studies
  • Risk Factors
  • Surveys and Questionnaires
  • Young Adult

Cite this

Psychiatric Genomic Consortium Major Depressive Disorder Working Group (2014). Applying polygenic risk scores to postpartum depression. Archives of womens mental health, 17(6), 519-528. https://doi.org/10.1007/s00737-014-0428-5
Psychiatric Genomic Consortium Major Depressive Disorder Working Group. / Applying polygenic risk scores to postpartum depression. In: Archives of womens mental health. 2014 ; Vol. 17, No. 6. pp. 519-528.
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Psychiatric Genomic Consortium Major Depressive Disorder Working Group 2014, 'Applying polygenic risk scores to postpartum depression' Archives of womens mental health, vol. 17, no. 6, pp. 519-528. https://doi.org/10.1007/s00737-014-0428-5

Applying polygenic risk scores to postpartum depression. / Psychiatric Genomic Consortium Major Depressive Disorder Working Group.

In: Archives of womens mental health, Vol. 17, No. 6, 12.2014, p. 519-528.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Applying polygenic risk scores to postpartum depression

AU - Byrne, Enda M

AU - Carrillo-Roa, Tania

AU - Penninx, Brenda W J H

AU - Sallis, Hannah M

AU - Viktorin, Alexander

AU - Chapman, Brett

AU - Henders, Anjali K

AU - Pergadia, Michele L

AU - Heath, Andrew C

AU - Madden, Pamela A F

AU - Sullivan, Patrick F

AU - Boschloo, Lynn

AU - van Grootheest, Gerard

AU - McMahon, George

AU - Lawlor, Debbie A

AU - Landén, Mikael

AU - Lichtenstein, Paul

AU - Magnusson, Patrik K E

AU - Evans, David M

AU - Montgomery, Grant W

AU - Boomsma, Dorret I

AU - Martin, Nicholas G

AU - Meltzer-Brody, Samantha

AU - Wray, Naomi R

AU - Psychiatric Genomic Consortium Major Depressive Disorder Working Group

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N2 - 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.

AB - 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.

KW - Adult

KW - Bipolar Disorder/genetics

KW - Depression, Postpartum/genetics

KW - Depressive Disorder, Major/genetics

KW - Female

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - Genotype

KW - Humans

KW - Logistic Models

KW - Male

KW - Multifactorial Inheritance

KW - Polymorphism, Single Nucleotide

KW - Retrospective Studies

KW - Risk Factors

KW - Surveys and Questionnaires

KW - Young Adult

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DO - 10.1007/s00737-014-0428-5

M3 - Article

VL - 17

SP - 519

EP - 528

JO - Archives of womens mental health

JF - Archives of womens mental health

SN - 1434-1816

IS - 6

ER -

Psychiatric Genomic Consortium Major Depressive Disorder Working Group. Applying polygenic risk scores to postpartum depression. Archives of womens mental health. 2014 Dec;17(6):519-528. https://doi.org/10.1007/s00737-014-0428-5