Elucidating the Genetic Basis of Social Interaction and Isolation

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Jul 5

PMID 29970889

Citations 74

Authors

Felix R Day

Ken K Ong

John R B Perry

Affiliations

Soon will be listed here.

Abstract

The negative impacts of social isolation and loneliness on health are well documented. However, little is known about their possible biological determinants. In up to 452,302 UK Biobank study participants, we perform genome-wide association study analyses for loneliness and regular participation in social activities. We identify 15 genomic loci (P < 5 × 10) for loneliness, and demonstrate a likely causal association between adiposity and increased susceptibility to loneliness and depressive symptoms. Further loci were identified for regular attendance at a sports club or gym (N = 6 loci), pub or social club (N = 13) or religious group (N = 18). Across these traits there was strong enrichment for genes expressed in brain regions that control emotional expression and behaviour. We demonstrate aetiological mechanisms specific to each trait, in addition to identifying loci that are pleiotropic across multiple complex traits. Further study of these traits may identify novel modifiable risk factors associated with social withdrawal and isolation.

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References

Gusev A, Ko A, Shi H, Bhatia G, Chung W, Penninx B . Integrative approaches for large-scale transcriptome-wide association studies. Nat Genet. 2016; 48(3):245-52. PMC: 4767558. DOI: 10.1038/ng.3506. View

Victor C, Bowling A . A longitudinal analysis of loneliness among older people in Great Britain. J Psychol. 2012; 146(3):313-31. DOI: 10.1080/00223980.2011.609572. View

Holt-Lunstad J, Smith T, Baker M, Harris T, Stephenson D . Loneliness and social isolation as risk factors for mortality: a meta-analytic review. Perspect Psychol Sci. 2015; 10(2):227-37. DOI: 10.1177/1745691614568352. View

Gao J, Davis L, Hart A, Sanchez-Roige S, Han L, Cacioppo J . Genome-Wide Association Study of Loneliness Demonstrates a Role for Common Variation. Neuropsychopharmacology. 2016; 42(4):811-821. PMC: 5312064. DOI: 10.1038/npp.2016.197. View

Day F, Helgason H, Chasman D, Rose L, Loh P, Scott R . Physical and neurobehavioral determinants of reproductive onset and success. Nat Genet. 2016; 48(6):617-623. PMC: 5238953. DOI: 10.1038/ng.3551. View

Elovainio M, Hakulinen C, Pulkki-Raback L, Virtanen M, Josefsson K, Jokela M . Contribution of risk factors to excess mortality in isolated and lonely individuals: an analysis of data from the UK Biobank cohort study. Lancet Public Health. 2017; 2(6):e260-e266. PMC: 5463031. DOI: 10.1016/S2468-2667(17)30075-0. View

Finucane H, Reshef Y, Anttila V, Slowikowski K, Gusev A, Byrnes A . Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types. Nat Genet. 2018; 50(4):621-629. PMC: 5896795. DOI: 10.1038/s41588-018-0081-4. View

Turley P, Walters R, Maghzian O, Okbay A, Lee J, Fontana M . Multi-trait analysis of genome-wide association summary statistics using MTAG. Nat Genet. 2018; 50(2):229-237. PMC: 5805593. DOI: 10.1038/s41588-017-0009-4. View

Holt-Lunstad J, Smith T, Layton J . Social relationships and mortality risk: a meta-analytic review. PLoS Med. 2010; 7(7):e1000316. PMC: 2910600. DOI: 10.1371/journal.pmed.1000316. View

10.

Burgess S, Butterworth A, Thompson J . Beyond Mendelian randomization: how to interpret evidence of shared genetic predictors. J Clin Epidemiol. 2015; 69:208-16. PMC: 4687951. DOI: 10.1016/j.jclinepi.2015.08.001. View

11.

Bulik-Sullivan B, Finucane H, Anttila V, Gusev A, Day F, Loh P . An atlas of genetic correlations across human diseases and traits. Nat Genet. 2015; 47(11):1236-41. PMC: 4797329. DOI: 10.1038/ng.3406. View

12.

Allen N, Sudlow C, Peakman T, Collins R . UK biobank data: come and get it. Sci Transl Med. 2014; 6(224):224ed4. DOI: 10.1126/scitranslmed.3008601. View

13.

Loh P, Tucker G, Bulik-Sullivan B, Vilhjalmsson B, Finucane H, Salem R . Efficient Bayesian mixed-model analysis increases association power in large cohorts. Nat Genet. 2015; 47(3):284-90. PMC: 4342297. DOI: 10.1038/ng.3190. View

14.

Finucane H, Bulik-Sullivan B, Gusev A, Trynka G, Reshef Y, Loh P . Partitioning heritability by functional annotation using genome-wide association summary statistics. Nat Genet. 2015; 47(11):1228-35. PMC: 4626285. DOI: 10.1038/ng.3404. View

15.

Zheng J, Erzurumluoglu A, Elsworth B, Kemp J, Howe L, Haycock P . LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis. Bioinformatics. 2016; 33(2):272-279. PMC: 5542030. DOI: 10.1093/bioinformatics/btw613. View

16.

Locke A, Kahali B, Berndt S, Justice A, Pers T, Day F . Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015; 518(7538):197-206. PMC: 4382211. DOI: 10.1038/nature14177. View

17.

Bowden J, Davey Smith G, Haycock P, Burgess S . Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator. Genet Epidemiol. 2016; 40(4):304-14. PMC: 4849733. DOI: 10.1002/gepi.21965. View

18.

Hyde C, Nagle M, Tian C, Chen X, Paciga S, Wendland J . Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nat Genet. 2016; 48(9):1031-6. PMC: 5706769. DOI: 10.1038/ng.3623. View