Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
26390830
TITLE
Genome-wide autozygosity is associated with lower general cognitive ability.
ABSTRACT
NlmCategory: UNASSIGNED
Inbreeding depression refers to lower fitness among offspring of genetic relatives. This reduced fitness is caused by the inheritance of two identical chromosomal segments (autozygosity) across the genome, which may expose the effects of (partially) recessive deleterious mutations. Even among outbred populations, autozygosity can occur to varying degrees due to cryptic relatedness between parents. Using dense genome-wide single-nucleotide polymorphism (SNP) data, we examined the degree to which autozygosity associated with measured cognitive ability in an unselected sample of 4854 participants of European ancestry. We used runs of homozygosity-multiple homozygous SNPs in a row-to estimate autozygous tracts across the genome. We found that increased levels of autozygosity predicted lower general cognitive ability, and estimate a drop of 0.6 s.d. among the offspring of first cousins (P=0.003-0.02 depending on the model). This effect came predominantly from long and rare autozygous tracts, which theory predicts as more likely to be deleterious than short and common tracts. Association mapping of autozygous tracts did not reveal any specific regions that were predictive beyond chance after correcting for multiple testing genome wide. The observed effect size is consistent with studies of cognitive decline among offspring of known consanguineous relationships. These findings suggest a role for multiple recessive or partially recessive alleles in general cognitive ability, and that alleles decreasing general cognitive ability have been selected against over evolutionary time.Molecular Psychiatry advance online publication, 22 September 2015; doi:10.1038/mp.2015.120.
DATE PUBLISHED
2015 Sep 22
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2015/04/01
revised 2015/05/23
accepted 2015/07/13
entrez 2015/09/23 06:00
pubmed 2015/09/24 06:00
medline 2015/09/24 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Howrigan DP Howrigan D P DP Stanley Center for Psychiatric Genetics, Broad Institute of Harvard and MIT, Cambridge Center, Cambridge, MA, USA.
Simonson MA Simonson M A MA Division of Data Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Davies G Davies G G Department of Psychology, University of Edinburgh, Edinburgh, UK.
Harris SE Harris S E SE Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.
Tenesa A Tenesa A A The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, UK.
Starr JM Starr J M JM Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
Liewald DC Liewald D C DC Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
Deary IJ Deary I J IJ Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
McRae A McRae A A Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
Wright MJ Wright M J MJ Queensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia.
Montgomery GW Montgomery G W GW Queensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia.
Hansell N Hansell N N Queensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia.
Martin NG Martin N G NG Queensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia.
Payton A Payton A A Centre for Integrated Genomic Medical Research, Institute of Population Health, University of Manchester, Manchester, UK.
Horan M Horan M M Centre for Clinical and Cognitive Neurosciences, Institute of Brain Behaviour and Mental Health, University of Manchester, Salford Royal NHS Foundation Trust, Salford, UK.
Ollier WE Ollier W E WE Centre for Integrated Genomic Medical Research, Institute of Population Health, University of Manchester, Manchester, UK.
Abdellaoui A Abdellaoui A A Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
Boomsma DI Boomsma D I DI EMGO+ Institute for Health and Care Research, Amsterdam, The Netherlands.
DeRosse P DeRosse P P Hofstra North Shore - LIJ School of Medicine, Departments of Psychiatry and Molecular Medicine, Hempstead, NY, USA.
Knowles EE Knowles E E M EE Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Glahn DC Glahn D C DC Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Djurovic S Djurovic S S Oslo University Hospital, Oslo, Norway.
Melle I Melle I I University of Oslo, Oslo, Norway.
Andreassen OA Andreassen O A OA University of Oslo, Oslo, Norway.
Christoforou A Christoforou A A Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
Steen VM Steen V M VM Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
Hellard SL Hellard S L SL Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
Sundet K Sundet K K Department of Psychology, University of Oslo, Oslo, Norway.
Reinvang I Reinvang I I Department of Psychology, University of Oslo, Oslo, Norway.
Espeseth T Espeseth T T Norwegian Center for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Oslo University Hospital, Oslo, Norway.
Lundervold AJ Lundervold A J AJ Kavli Research Centre for Aging and Dementia, Haraldsplass Deaconess Hospital, Bergen, Norway.
Giegling I Giegling I I Department of Psychiatry, University of Halle, Halle, Germany.
Konte B Konte B B Department of Psychiatry, University of Halle, Halle, Germany.
Hartmann AM Hartmann A M AM Department of Psychiatry, University of Halle, Halle, Germany.
Rujescu D Rujescu D D Department of Psychiatry, University of Halle, Halle, Germany.
Roussos P Roussos P P James J. Peters VA Medical Center, Mental Illness Research Education and Clinical Center (MIRECC), Bronx, NY, USA.
Giakoumaki S Giakoumaki S S Department of Psychology, University of Crete, Rethymno, Crete, Greece.
Burdick KE Burdick K E KE Department of Psychiatry, Friedman Brain Institute, Department of Genetics and Genomic Sciences, and Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Bitsios P Bitsios P P Computational Medicine Laboratory, Institute of Computer Science at FORTH, Heraklion, Greece.
Donohoe G Donohoe G G School of Psychology, National University of Ireland Galway, Galway, Ireland.
Corley RP Corley R P RP Institute for Behavioral Genetics, University of Colorado at Boulder, Boulder, CO, USA.
Visscher PM Visscher P M PM University of Queensland Diamantina Institute, The University of Queensland, Princess Alexandra Hospital, Brisbane, QLD, Australia.
Pendleton N Pendleton N N Centre for Integrated Genomic Medical Research, Institute of Population Health, University of Manchester, Manchester, UK.
Malhotra AK Malhotra A K AK Hofstra North Shore - LIJ School of Medicine, Departments of Psychiatry and Molecular Medicine, Hempstead, NY, USA.
Neale BM Neale B M BM Stanley Center for Psychiatric Genetics, Broad Institute of Harvard and MIT, Cambridge Center, Cambridge, MA, USA.
Lencz T Lencz T T Hofstra North Shore - LIJ School of Medicine, Departments of Psychiatry and Molecular Medicine, Hempstead, NY, USA.
Keller MC Keller M C MC Department of Psychology, University of Colorado at Boulder, Boulder, CO, USA.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2015
MONTH: Sep
DAY: 22
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5578
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
JOURNAL ARTICLE
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