Behavior Genetics

, Volume 43, Issue 6, pp 455–467 | Cite as

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

  • Abdel Abdellaoui
  • Jouke-Jan Hottenga
  • Xiangjun Xiao
  • Paul Scheet
  • Erik A. Ehli
  • Gareth E. Davies
  • James J. Hudziak
  • Dirk J. A. Smit
  • Meike Bartels
  • Gonneke Willemsen
  • Andrew Brooks
  • Patrick F. Sullivan
  • Johannes H. Smit
  • Eco J. de Geus
  • Brenda W. J. H. Penninx
  • Dorret I. Boomsma
Original Research

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 relate Froh 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. All Froh analyses included adjustment for ancestry-informative principal components (PCs) and geographic factors. Religious affiliation was significantly associated with autozygosity, showing that Froh 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 lower Froh 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 with Froh, 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.

Keywords

Autozygosity Runs of homozygosity Major depressive disorder Religion Population stratification Assortative mating 

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Abdel Abdellaoui
    • 1
    • 2
  • Jouke-Jan Hottenga
    • 1
  • Xiangjun Xiao
    • 3
  • Paul Scheet
    • 3
  • Erik A. Ehli
    • 4
  • Gareth E. Davies
    • 4
  • James J. Hudziak
    • 5
  • Dirk J. A. Smit
    • 1
  • Meike Bartels
    • 1
  • Gonneke Willemsen
    • 1
  • Andrew Brooks
    • 6
  • Patrick F. Sullivan
    • 7
  • Johannes H. Smit
    • 8
    • 9
  • Eco J. de Geus
    • 1
    • 2
    • 8
  • Brenda W. J. H. Penninx
    • 2
    • 8
    • 9
  • Dorret I. Boomsma
    • 1
    • 2
    • 8
  1. 1.Department of Biological Psychology, Netherlands Twin RegisterVU University AmsterdamAmsterdamThe Netherlands
  2. 2.Neuroscience Campus AmsterdamAmsterdamThe Netherlands
  3. 3.Department of EpidemiologyUniversity of Texas M.D. Anderson Cancer CenterHoustonUSA
  4. 4.Avera Institute for Human Genetics, Avera Behavioral Health CenterSioux FallsUSA
  5. 5.College of Medicine, University of VermontBurlingtonUSA
  6. 6.Department of Genetics, RutgersThe State University of New JerseyPiscatawayUSA
  7. 7.Department of GeneticsUniversity of North CarolinaChapel HillUSA
  8. 8.EMGO Institute for Health and Care ResearchAmsterdamThe Netherlands
  9. 9.Department of PsychiatryVU University Medical CenterAmsterdamThe Netherlands

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