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Phenome-wide investigation of health outcomes associated with genetic predisposition to loneliness

dc.contributor.authorSealock, Julia
dc.contributor.authorDennis, Jessica
dc.contributor.authorDavis, Lea K.
dc.date.accessioned2020-09-04T19:01:10Z
dc.date.available2020-09-04T19:01:10Z
dc.date.issued2019-11-15
dc.identifier.citationAbdellaoui, A., Sanchez-Roige, S., Sealock, J., Treur, J. L., Dennis, J., Fontanillas, P., Elson, S., 23andme Research Team, Nivard, M. G., Ip, H. F., van der Zee, M., Baselmans, B., Hottenga, J. J., Willemsen, G., Mosing, M., Lu, Y., Pedersen, N. L., Denys, D., Amin, N., M van Duijn, C., … Boomsma, D. I. (2019). Phenome-wide investigation of health outcomes associated with genetic predisposition to loneliness. Human molecular genetics, 28(22), 3853–3865. https://doi.org/10.1093/hmg/ddz219en_US
dc.identifier.issn0964-6906
dc.identifier.urihttp://hdl.handle.net/1803/15607
dc.descriptionOnly Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935385/en_US
dc.description.abstractHumans are social animals that experience intense suffering when they perceive a lack of social connection. Modern societies are experiencing an epidemic of loneliness. Although the experience of loneliness is universally human, some people report experiencing greater loneliness than others. Loneliness is more strongly associated with mortality than obesity, emphasizing the need to understand the nature of the relationship between loneliness and health. Although it is intuitive that circumstantial factors such as marital status and age influence loneliness, there is also compelling evidence of a genetic predisposition toward loneliness. To better understand the genetic architecture of loneliness and its relationship with associated outcomes, we extended the genome-wide association study meta-analysis of loneliness to 511280 subjects, and detect 19 significant genetic variants from 16 loci, including four novel loci, as well as 58 significantly associated genes. We investigated the genetic overlap with a wide range of physical and mental health traits by computing genetic correlations and by building loneliness polygenic scores in an independent sample of 18498 individuals with EHR data to conduct a PheWAS with. A genetic predisposition toward loneliness was associated with cardiovascular, psychiatric, and metabolic disorders and triglycerides and high-density lipoproteins. Mendelian randomization analyses showed evidence of a causal, increasing, the effect of both BMI and body fat on loneliness. Our results provide a framework for future studies of the genetic basis of loneliness and its relationship to mental and physical health.en_US
dc.description.sponsorshipThe National Institutes of Health (NIH, R01AG033590 to JC); the Royal Netherlands Academy of Science Professor Award (PAH/6635 to NTR: DIB). Data collection and genotyping in NTR by the Netherlands Organization for Scientific Research (90461-090, 85-10-002, 904-61-193, 480-04-004, 400-05-717, Spi-56464-14192 and 480-15-001/674); Biobanking and Biomolecular Resources Research Infrastructure (BBMRI -NL, 184.021.007 and 184.033.111); the Avera Institute for Human Genetics, Sioux Falls, South Dakota (USA) and the National Institutes of Health (NIH, R01D0042157-01A); the NIMH Grand Opportunity grants (1RC2MH089951-01 and 1RC2 MH089995-01). A Rubicon grant from the Netherlands Organization for Scientific Research (NWO; grant number 446-16-009 to J.L.T.); NIMH (grant 5R01MH113362-02 to L.K.D.); NIH training grant (2T32GM080178 to J.M.S). The Frontiers of Innovation Scholars Program (FISP; #3-P3029 to S.S.-R.); the Interdisciplinary Research Fellowship in NeuroAIDS (IRFN; MH081482); a pilot award from DA037844 and 2018 NARSAD Young Investigator Grant (27676); the California Tobacco-Related Disease Research Program (TRDRP; Grant Number 28IR-0070 to S.S.-R. and A.A.P.); Institutional funding (the 1S10RR025141-01 instrumentation award, and by the CTSA grant UL1TR000445 from NCATS/NIH to Medical Center's BioVU); NIH (additional funding through grants P50GM115305 and U19HL065962); Part of the computations for this paper was performed on Cartesius (grant `Population scale genetic analysis'; NWO rekentijd: 16332).en_US
dc.language.isoen_USen_US
dc.publisherHuman Molecular Geneticsen_US
dc.rightsCopyright © The Author(s) 2019. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.source.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935385/
dc.titlePhenome-wide investigation of health outcomes associated with genetic predisposition to lonelinessen_US
dc.typeArticleen_US
dc.identifier.doi10.1093/hmg/ddz219


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