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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
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Official URL: http://dx.doi.org/10.1038/s41588-018-0320-8
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 | ||||||||
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| 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 |
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| Journal or Publication Title: | Nature Genetics | ||||||||
| Publisher: | Nature Publishing Group | ||||||||
| ISSN: | 1061-4036 | ||||||||
| Official Date: | March 2019 | ||||||||
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| 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 | ||||||||
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