Variants in the ATP-Binding Cassette Transporter (ABCA7), Apolipoprotein E ϵ4, and the Risk of Late-Onset Alzheimer Disease in African Americans

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Abstract
Late-onset Alzheimer disease (LOAD) is the most common cause of dementia, increasing in frequency from 1% at age 65 years to more than 30% for people older than 80 years.1 As much as 20% of the disease-attributable risk is related to the ϵ4 variant in APOE.2 A series of large genome-wide association studies (GWASs) identified several additional variants that affect disease susceptibility in non-Hispanic whites of European ancestry, including CR1, CLU, PICALM, BIN1, CD2AP, CD33, EPHA1, MS4A6A/MS4E4, and ABCA7.3-7 In addition, SORL1 was identified as a susceptibility gene in candidate gene and functional studies.8,9 However, LOAD heritability estimates are high (h2 ≈ 60%-80%), and a large part of the genetic contribution to LOAD remains unexplained.10