Family-based association analysis by the Pedigree Disequilibrium Test (PDT) demonstrated that the indel was associated with alcohol dependence (P = 0.01). The minor allele, with the net additional 830 bp, was overtransmitted to affected individuals (265 transmissions versus 235 non-transmissions) and overtransmitted to the affected sibling in a discordant sibling pair (495 transmissions to the affected sibling; 453 transmissions to the unaffected sibling). Reanalyzing the data after coding as ‘unknown’ individuals who were not alcohol dependent but were dependent on other illicit drugs (in case there was shared genetic vulnerability at this locus) yielded a similar result (P = 0.02). Comparing the pattern of association results previously reported for SNPs (17) with that of LD as measured by r2 (Fig. 4), we found that four of the five SNPs for which r2 with the indel was >35% were significant and the fifth was marginal; in contrast, only one of the eight SNPs for which r2 with the indel was lower (<35%) was significant and one was marginal.
