∼1.7Mb away from our markers rs7590720 and rs1344694. The LR to alcohol is an endophenotype related to heavy drinking and alcohol problems.54 It is genetically influenced in both animals55-57 and humans58,59 with an estimated heritability in humans of between 40-50%60. Two further linkage studies of the COGA project61,62 reported linkage with LOD scores of 3.28 and 3.0, respectively, between the same marker D2S434 and the P3(00) component of the event related potential (ERP). Heritability of the P3 amplitude ranges between 50-80% (for review see 62) and P3 deficits have been repeatedly reported to be a strong vulnerability factor for alcohol dependence, especially in males with a high familial loading of alcohol dependence.63,64 In a linkage scan conducted by Hill et al.65 in 330 members from 65 families with a high density of alcohol dependence, linkage to 2q35 with marker D2S2382 was identified. This marker is located only ∼0.2Mb from our two main SNPs. A LOD score of 3.68 was observed in a four-parameter model which included measurement of age, gender and alcohol dependence along with measurement of constraint - a personality construct66 which appears to overlap with risk taking behaviour.
