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Association Between Autozygosity and Major Depression: Stratification Due to Religious Assortment

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Abstract

The effects of inbreeding on the health of offspring can be studied by measuring genome-wide autozygosity as the proportion of the genome in runs of homozygosity (Froh) and relateFroh to outcomes such as psychiatric phenotypes. To successfully conduct these studies, the main patterns of variation for genome-wide autozygosity between and within populations should be well understood and accounted for. Within population variation was investigated in the Dutch population by comparing autozygosity between religious and non-religious groups. The Netherlands have a history of societal segregation and assortment based on religious affiliation, which may have increased parental relatedness within religious groups. Religion has been associated with several psychiatric phenotypes, such as major depressive disorder (MDD). We investigated whether there is an association between autozygosity and MDD, and the extent to which this association can be explained by religious affiliation. AllFroh analyses included adjustment for ancestry-informative principal components (PCs) and geographic factors. Religious affiliation was significantly associated with autozygosity, showing thatFroh has the ability to capture within population differences that are not captured by ancestry-informative PCs or geographic factors. The non-religious group had significantly lowerFroh values and significantly more MDD cases, leading to a nominally significant negative association between autozygosity and depression. After accounting for religious affiliation, MDD was not associated withFroh, indicating that the relation between MDD and inbreeding was due to stratification. This study shows how past religious assortment and recent secularization can have genetic consequences in a relatively small country. This warrants accounting for the historical social context and its effects on genetic variation in association studies on psychiatric and other related traits.

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Acknowledgments

Funding was obtained from the Netherlands Organization for Scientific Research (NWO: MagW/ZonMW Grants 904-61-090, 985-10-002,904-61-193,480-04-004, 400-05-717, Addiction-31160008 Middelgroot-911-09-032, Spinozapremie 56-464-14192, Geestkracht program grant 10-000-1002), Center for Medical Systems Biology (CSMB, NWO Genomics), NBIC/BioAssist/RK(2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL, 184.021.007), the VU University’s Institute for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam (NCA), the European Science Foundation (ESF, EU/QLRT-2001-01254), the European Community’s Seventh Framework Program (FP7/2007-2013), ENGAGE (HEALTH-F4-2007-201413); the European Science Council (ERC Advanced, 230374), Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera Institute for Human Genetics, Sioux Falls, South Dakota (USA) and the National Institutes of Health (R01-HD042157-01A). Part of the genotyping was funded by the Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health, the (NIMH, MH081802) and by the Grand Opportunity grants 1RC2MH089951-01 and 1RC2 MH089995-01 from the NIMH. AA was supported by CSMB/NCA. Statistical analyses were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org), which is financially supported by the Netherlands Scientific Organization (NWO 480-05-003), the Dutch Brain Foundation, and the department of psychology and education of the VU University Amsterdam.

Author information

Authors and Affiliations

  1. Department of Biological Psychology, Netherlands Twin Register, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands

    Abdel Abdellaoui, Jouke-Jan Hottenga, Dirk J. A. Smit, Meike Bartels, Gonneke Willemsen, Eco J. de Geus & Dorret I. Boomsma

  2. Neuroscience Campus Amsterdam, Amsterdam, The Netherlands

    Abdel Abdellaoui, Eco J. de Geus, Brenda W. J. H. Penninx & Dorret I. Boomsma

  3. Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Xiangjun Xiao & Paul Scheet

  4. Avera Institute for Human Genetics, Avera Behavioral Health Center, Sioux Falls, SD, USA

    Erik A. Ehli & Gareth E. Davies

  5. College of Medicine, University of Vermont, Burlington, VT, USA

    James J. Hudziak

  6. Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ, USA

    Andrew Brooks

  7. Department of Genetics, University of North Carolina, Chapel Hill, NC, USA

    Patrick F. Sullivan

  8. EMGO Institute for Health and Care Research, Amsterdam, The Netherlands

    Johannes H. Smit, Eco J. de Geus, Brenda W. J. H. Penninx & Dorret I. Boomsma

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

    Johannes H. Smit & Brenda W. J. H. Penninx

Authors
  1. Abdel Abdellaoui

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  2. Jouke-Jan Hottenga

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  3. Xiangjun Xiao

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  4. Paul Scheet

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  5. Erik A. Ehli

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  6. Gareth E. Davies

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  7. James J. Hudziak

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  8. Dirk J. A. Smit

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  9. Meike Bartels

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  10. Gonneke Willemsen

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  11. Andrew Brooks

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  12. Patrick F. Sullivan

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  13. Johannes H. Smit

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  14. Eco J. de Geus

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  15. Brenda W. J. H. Penninx

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  16. Dorret I. Boomsma

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Corresponding author

Correspondence toAbdel Abdellaoui.

Additional information

Edited by John K. Hewitt.

Appendices

Appendix 1

See Table 6.

Table 6 Regression coefficients (p values between brackets) for each of the predictors included in the linear regressions

Appendix 2

See Table 7.

Table 7 Regression coefficients (p values between brackets) for each of the predictors included in the linear regressions of the MDD analyses

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Abdellaoui, A., Hottenga, JJ., Xiao, X.et al. Association Between Autozygosity and Major Depression: Stratification Due to Religious Assortment.Behav Genet43, 455–467 (2013). https://doi.org/10.1007/s10519-013-9610-1

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