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Purpose: To investigate the association between social isolation and loneliness, how they relate to depression, and whether these associations are explained by genetic influences.Methods: We used data from the age-18 wave of the Environmental Risk Longitudinal Twin Study, a birth cohort of 1116 same-sex twin pairs born in England and Wales in 1994 and 1995. Participants reported on their levels of social isolation, loneliness and depressive symptoms. We conducted regression analyses to test the differential associations of isolation and loneliness with depression. Using the twin study design, we estimated the proportion of variance in each construct and their covariance that was accounted for by genetic and environmental factors.Results: Social isolation and loneliness were moderately correlated (r = 0.39), reflecting the separateness of these constructs, and both were associated with depression. When entered simultaneously in a regression analysis, loneliness was more robustly associated with depression. We observed similar degrees of genetic influence on social isolation (40 %) and loneliness (38 %), and a smaller genetic influence on depressive symptoms (29 %), with the remaining variance accounted for by the non-shared environment. Genetic correlations of 0.65 between isolation and loneliness and 0.63 between loneliness and depression indicated a strong role of genetic influences in the co-occurrence of these phenotypes.Conclusions: Socially isolated young adults do not necessarily experience loneliness. However, those who are lonely are often depressed, partly because the same genes influence loneliness and depression. Interventions should not only aim at increasing social connections but also focus on subjective feelings of loneliness. [ABSTRACT FROM AUTHOR]