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Multivariate genome-wide analyses of the well-being spectrum

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BIOS consortium ; Social Science Genetic Association Consortium (Including: Baselmans, Bart M. L., Jansen, Rick, Ip, Hill F., van Dongen, Jenny, Abdellaoui, Abdel, van de Weijer, Margot P., Bao, Yanchun, Smart, Melissa, Kumari, Meena, Willemsen, Gonneke, Hottenga, Jouke-Jan, Boomsma, Dorret I., de Geus, Eco J. C., Nivard, Michel G. and Bartels, Meike). (2019) Multivariate genome-wide analyses of the well-being spectrum. Nature Genetics, 51 (3). pp. 445-451. doi:10.1038/s41588-018-0320-8

Research output not available from this repository, contact author.
Official URL: http://dx.doi.org/10.1038/s41588-018-0320-8

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Abstract

We introduce two novel methods for multivariate genome-wide-association meta-analysis (GWAMA) of related traits that correct for sample overlap. A broad range of simulation scenarios supports the added value of our multivariate methods relative to univariate GWAMA. We applied the novel methods to life satisfaction, positive affect, neuroticism, and depressive symptoms, collectively referred to as the well-being spectrum (Nobs = 2,370,390), and found 304 significant independent signals. Our multivariate approaches resulted in a 26% increase in the number of independent signals relative to the four univariate GWAMAs and in an ~57% increase in the predictive power of polygenic risk scores. Supporting transcriptome- and methylome-wide analyses (TWAS and MWAS, respectively) uncovered an additional 17 and 75 independent loci, respectively. Bioinformatic analyses, based on gene expression in brain tissues and cells, showed that genes differentially expressed in the subiculum and GABAergic interneurons are enriched in their effect on the well-being spectrum.

Item Type: Journal Article
Divisions: Faculty of Medicine > Warwick Medical School > Health Sciences
Faculty of Medicine > Warwick Medical School > Health Sciences > Mental Health and Wellbeing
Faculty of Medicine > Warwick Medical School
Journal or Publication Title: Nature Genetics
Publisher: Nature Publishing Group
ISSN: 1061-4036
Official Date: March 2019
Dates:
DateEvent
March 2019Published
14 January 2019Available
27 November 2018Accepted
Volume: 51
Number: 3
Page Range: pp. 445-451
DOI: 10.1038/s41588-018-0320-8
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Contributors:
ContributionNameContributor ID
ResearcherCappuccio, Francesco13620

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