Genome-Wide Association Study of Loneliness Demonstrates a Role for Common Variation

Jianjun Gao, Lea K Davis, Amy B Hart, Sandra Sanchez-Roige, Lide Han, John T Cacioppo, Abraham A Palmer

Loneliness is a complex biological trait that has been associated with numerous negative health outcomes. The measurement and environmental determinants of loneliness are well understood, but its genetic basis is not. Previous studies have estimated the heritability of loneliness between 37-55% using twins and family-based approaches, and have explored the role of specific candidate genes. We used genotypic and phenotypic data from 10 760 individuals aged 50 and over that were collected by the Health and Retirement Study (HRS) to perform the first genome-wide association study of loneliness. No associations reached genome-wide significance (p>5 × 10(-8)). Furthermore, none of the previously published associations between variants within candidate genes (BDNF, OXTR, RORA, GRM8, CHRNA4, IL-1A, CRHR1, MTHFR, DRD2, APOE) and loneliness were replicated (p>0.05), despite our much larger sample size. We estimated the chip heritability of loneliness and examined co-heritability between loneliness and several personality and psychiatric traits. Our estimates of chip heritability (14-27%) support a role for common genetic variation. We identified strong genetic correlations between loneliness, neuroticism and a scale of 'depressive symptoms'. We also identified weaker evidence for co-heritability with extraversion, schizophrenia, bipolar disorder and major depressive disorder. We conclude that loneliness, as defined in this study, is a modestly heritable trait that has a highly polygenic genetic architecture. The co-heritability between loneliness and neuroticism may reflect the role of negative affectivity, which is common to both traits. Our results also reflect the value of studies that probe the common genetic basis of salutary social bonds and clinically defined psychiatric disorders.Neuropsychopharmacology accepted article preview online, 15 September 2016. doi:10.1038/npp.2016.197.