OBJECTIVE: Loneliness is an aversive response to a discrepancy between desired and actual social relationships and correlates with personality. We investigate the relationship of loneliness and personality in twin-family and molecular genetic data. METHOD: Phenotypic correlations between loneliness and the Big Five personality traits were estimated in 29,625 adults, and in a group with genome-wide genotype data (N=4,222), genetic correlations were obtained. We explored whether genetic correlations may reflect causal relationships by investigating within monozygotic twin-pair differences (Npairs =2,662), by longitudinal within-subject changes in personality and loneliness (N=4,260-9,238 longitudinal comparisons), and by longitudinal cross-lagged panel analyses (N=15,628). Finally, we tested whether genetic correlations were due to cross-trait assortative mating (Nspouse-pairs =4,436). RESULTS: The strongest correlations with loneliness were observed for neuroticism (r=.55) and extraversion (r=-.33). Only neuroticism showed a high correlation with loneliness independent of other personality traits (r=.50), so follow-up analyses focused on neuroticism. The genetic correlation between loneliness and neuroticism from genotyped variants was .71; a significant reciprocal causal relationship and non-significant cross-trait assortative mating imply that this is at least partly due to mediated pleiotropy. CONCLUSION: We show that the relationship between loneliness and personality is largely explained by its relationship with neuroticism, which is substantially genetic in nature. This article is protected by copyright. All rights reserved.