Gene-finding studies for higher-order personality traits have focused mainly on neuroticism, because of its association with anxiety and depression. Identifying genetic variants associated with neuroticism, but also with extraversion, has proven difficult. Suggestive linkage has been reported for several chromosomal regions with only few replications.21, 22, 23, 24, 25, 26, 27 Candidate studies have reported associations with markers within several genes,28, 29, 30, 31, 32 but again, replication generally failed.33, 34, 35 To date, a number of genome-wide association studies (GWAS) for higher-order personality traits have been published.36, 37, 38, 39, 40 None of them, however, has reported genome-wide significant associations between neuroticism/extraversion and markers. The dilemma of moderate to high heritability estimates of which only a small proportion can be explained by markers has been expressed as ‘the case of the missing heritability'.41, 42
