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Applying polygenic risk scores to postpartum depression

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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.

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Acknowledgments

Australia: This research was directly supported by the Australian Research Council (FT0991360) and the Australian National Health and Medical Research Council (613608). Support was received by the National Institutes of Health: DA12854, AA13320, AA13321, DA019951. We acknowledge Professor Matthew Brown for genotyping undertaken at the University of Queensland Centre for Clinical Genomics, housed at UQ’s Diamantina Institute. A portion of the statistical analyses were carried out on the QIMR GenEpi Cluster, which is financially supported by contributions from grants from the Australian National Health and Medical Research Council (389892; 496682; 496688; 496739; 613672). We thank the ATR twins for their continued participation. We also thank Dixie Statham, Bronwyn Morris and Megan Ferguson for coordinating the data collection for the twins; David Smyth, Olivia Zheng and Harry Beeby for data management; Lisa Bowdler, Steven Crooks (DNA processing) and Sarah Medland, Dale Nyholt and Scott Gordon (imputation and genotyping QC).

NTR/NESDA: The Netherlands Study of Depression and Anxiety (NESDA) and The Netherlands Twin Register (NTR) were funded by The Netherlands Organization for Scientific Research (MagW/ZonMW grants 904-61-090, 985-10-002,904-61-193,480-04-004, 400-05-717, 912-100-20; Spinozapremie 56-464-14192; Geestkracht program grant 10-000-1002); the Center for Medical Systems Biology (CMSB2; NWO Genomics), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL), VU University EMGO+ Institute for Health and Care Research and the Neuroscience Campus Amsterdam, NBIC/BioAssist/RK (2008.024); the European Science Foundation (EU/QLRT-2001-01254); the European Community’s Seventh Framework Program (FP7/2007-2013); ENGAGE (HEALTH-F4-2007-201413) and the European Science Council (ERC, 230374). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health, by the US National Institute of Mental Health (RC2 MH089951, PI Sullivan and 1RC2 MH089995 PI Hudziak) and as part of the American Recovery and Reinvestment Act of 2009. We acknowledge Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06) and the Avera Institute, Sioux Falls, South Dakota (USA).

ALSPAC: A grant from the Wellcome Trust (WT088806) provided funds for the ALSPAC genome-wide data used in this study and for G.M’s salary at the time analyses with these data were undertaken. The UK Medical Research Council and the Wellcome Trust (Grant ref: 092731) and the University of Bristol provide core support for ALSPAC. H.M.S. was funded by a Wellcome Trust 4-year PhD studentship in molecular, genetic and life course epidemiology (WT099871MA). H.M.S, D.A.L, and D.M.E work in a unit that receives research funds from the MRC. The authors are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses

STR: The Swedish Twin Registry is supported by the Swedish Department of Higher Education, the European Commission European Network for Genetic and Genomic Epidemiology (ENGAGE: 7th Framework Program (FP7/2007-2013)/grant agreement HEALTH-F4-2007-201413 and GenomEUtwin: 5th Framework program “Quality of Life and Management of the Living Resources” Grant QLG2-CT-2002-01254); the NIH (DK U01-066134); the Swedish Research Council (M-2005–1112 and 2009–2298); the Swedish Foundation for Strategic Research (ICA08-0047); the Jan Wallander and Tom Hedelius Foundation; and the Swedish Council for Working Life and Social Research.

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Authors and Affiliations

  1. Queensland Brain Institute, The University of Queensland, Upland Road, St. Lucia, Brisbane, QLD, 4072, Australia

    Enda M. Byrne, Tania Carrillo-Roa & Naomi R. Wray

  2. Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands

    Brenda W. J. H. Penninx, Lynn Boschloo & Gerard van Grootheest

  3. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK

    Hannah M. Sallis, George McMahon, Debbie A. Lawlor & David M. Evans

  4. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden

    Alexander Viktorin, Mikael Landén, Paul Lichtenstein & Patrik K. E. Magnusson

  5. Queensland Institute of Medical Research, Brisbane, Australia

    Enda M. Byrne, Tania Carrillo-Roa, Brett Chapman, Anjali K. Henders, Grant W. Montgomery & Nicholas G. Martin

  6. Department of Psychiatry, Washington University, St. Louis, MO, USA

    Michele L. Pergadia, Andrew C. Heath & Pamela A. F. Madden

  7. Department of Genetics and Psychiatry, University of North Carolina at Chapel Hill, CB# 7264, 5097 Genomic Medicine, Chapel Hill, NC, 27599-27264, USA

    Patrick F. Sullivan

  8. Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands

    Dorret I. Boomsma

  9. Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7570, USA

    Samantha Meltzer-Brody

  10. School of Social and Community Medicine, University of Bristol, Bristol, UK

    Hannah M. Sallis, George McMahon, Debbie A. Lawlor & David M. Evans

  11. University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia

    David M. Evans

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  1. Enda M. Byrne
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  2. Tania Carrillo-Roa
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  8. Michele L. Pergadia
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  9. Andrew C. Heath
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  10. Pamela A. F. Madden
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  11. Patrick F. Sullivan
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  12. Lynn Boschloo
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  18. Patrik K. E. Magnusson
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  20. Grant W. Montgomery
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  21. Dorret I. Boomsma
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  22. Nicholas G. Martin
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  23. Samantha Meltzer-Brody
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Psychiatric Genomic Consortium Major Depressive Disorder Working Group

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Correspondence to Enda M. Byrne.

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Byrne, E.M., Carrillo-Roa, T., Penninx, B.W.J.H. et al. Applying polygenic risk scores to postpartum depression. Arch Womens Ment Health 17, 519–528 (2014). https://doi.org/10.1007/s00737-014-0428-5

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  • DOI: https://doi.org/10.1007/s00737-014-0428-5

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