Loss-of-function variants in ABCA7 confer risk of Alzheimer's disease

• Published in: Nature genetics Vol. 47; no. 5; pp. 445 - 447
• Main Authors: Steinberg, Stacy, Stefansson, Hreinn, Jonsson, Thorlakur, Johannsdottir, Hrefna, Ingason, Andres, Helgason, Hannes, Sulem, Patrick, Magnusson, Olafur Th, Gudjonsson, Sigurjon A, Unnsteinsdottir, Unnur, Kong, Augustine, Helisalmi, Seppo, Soininen, Hilkka, Lah, James J, Aarsland, Dag, Fladby, Tormod, Ulstein, Ingun D, Djurovic, Srdjan, Sando, Sigrid B, White, Linda R, Knudsen, Gun-Peggy, Westlye, Lars T, Selbæk, Geir, Giegling, Ina, Hampel, Harald, Hiltunen, Mikko, Levey, Allan I, Andreassen, Ole A, Rujescu, Dan, Jonsson, Palmi V, Bjornsson, Sigurbjorn, Snaedal, Jon, Stefansson, Kari
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.05.2015; Nature Publishing Group
• Subjects: 45/23; 631/208/205/2138; Agriculture; Alzheimer Disease - genetics; Alzheimer's disease; Animal Genetics and Genomics; ATP-Binding Cassette Transporters - genetics; Biomedical and Life Sciences; Biomedicine; brief-communication; Cancer Research; Case-Control Studies; Cholesterol; Gene Function; Genetic aspects; Genetic Association Studies; Genetic Predisposition to Disease; Genetic variation; Haplotypes; Health aspects; Human Genetics; Humans; Medicin och hälsovetenskap; Membrane proteins; Mutation; Properties; Risk; Risk factors; Rodents; Sequence Analysis, DNA; Studies
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.3246

Stacy Steinberg, Hreinn Stefansson, Thorlakur Jonsson and colleagues found that rare variants predicted to alter the function of ABCA7 are associated with risk of Alzheimer's disease. The association was found in Iceland and replicated in northern Europe and the United States. We conducted a search for rare, functional variants altering susceptibility to Alzheimer's disease that exploited knowledge of common variants associated with the same disease. We found that loss-of-function variants in ABCA7 confer risk of Alzheimer's disease in Icelanders (odds ratio (OR) = 2.12, P = 2.2 × 10 −13 ) and discovered that the association replicated in study groups from Europe and the United States (combined OR = 2.03, P = 6.8 × 10 −15 ).