These two markers are located ∼5kb apart in chromosomal region 2q35, which has been implicated in alcohol dependence through previous linkage studies. Linkage to this region was found in a genome-wide search in 2282 individuals from 262 families with a high density of alcohol dependence by the Collaborative Study on the Genetics of Alcoholism (COGA).52 Near the microsatellite D2S1371, the highest LOD score for comorbid alcoholism and depression phenotype was 4.12 (this LOD score however, was only obtained in one dataset, i.e. in the replication dataset, while in the initial and combined datasets the LOD scores were 0.00 and 2.16, respectively).52 Marker D2S1371 is located ∼1.4Mb away from rs7590720 and rs1344694. Another COGA project53 found linkage with a maximum LOD score of 2.4 between a low level of response (LR) to alcohol and the microsatellite marker D2S434 which is only ∼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.
