Elucidating the genetic basis of social interaction and isolation

• Published in: Nature communications Vol. 9; no. 1; pp. 2457 - 6
• Main Authors: Day, Felix R., Ong, Ken K., Perry, John R. B.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.07.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 45/43; 631/208/205; 631/208/205/2138; 631/378/3919; 692/499; Adipose tissue; Adult; Brain; Depression - genetics; Depression - psychology; Emotional behavior; Female; Gene expression; Genome, Human - genetics; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Humanities and Social Sciences; Humans; Interpersonal Relations; Loci; Loneliness; Loneliness - psychology; Male; Mental depression; multidisciplinary; Polymorphism, Single Nucleotide; Risk analysis; Risk Factors; Science; Science (multidisciplinary); Social factors; Social interactions
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-04930-1

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 −8 ) 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. Little is known about the genetic determinants of social isolation and loneliness despite their well-established importance for health. Here, using multi-trait GWAS, Day et al. identify 15 genomic loci for loneliness and further show a bidirectional causal relationship between BMI and loneliness by MR.