An intergenic variant on chromosome 3, rs2168784, emerged as the SNP most significantly associated with age at onset of AD (MAF = 0.11, HR = 1.46, P = 4.99 × 10−9). The results of Cox hazard analysis indicated that the incidence of AD in carriers of the rs2168784 minor allele was 1.5 times greater than the subjects homozygous for the major allele. Twenty one percent of subjects were carriers of the minor allele of rs2168784, 47% of whom were diagnosed with AD. In this high-risk sample, the cumulative incidence plots indicate that by the age of 20 years, nearly 30% of the subjects homozygous for the minor allele of rs2168784 met criteria of AD. In comparison, only 19% of subjects homozygous for the major allele were diagnosed with AD by age 20 (Fig. 3(a). This SNP was also associated with AD symptom count (p = 4.1 × 10−6) and DSM-IV AD (p = 2.6 × 10−7) in the same sample of COGA families. Although rs2168784 has a variable MAF across populations the frequency in unrelated individuals from the COGA families
