Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

IntroductionThe genetic architecture of Alzheimer's disease (AD) is only partially understood.MethodsWe conducted an association study for AD using whole sequence data from 507 genetically enriched AD cases (i.e., cases having close relatives affected by AD) and 4917 cognitively healthy controls of European ancestry (EA) and 172 enriched cases and 179 controls of Caribbean Hispanic ancestry. Confirmation of top findings from stage 1 was sought in two family-based genome-wide association study data sets and in a whole genome-sequencing data set comprising members from 42 EA and 115 Caribbean Hispanic families.ResultsWe identified associations in EAs with variants in 12 novel loci. The most robust finding is a rare CASP7 missense variant (rs116437863; P = 2.44 × 10-10) which improved when combined with results from stage 2 data sets (P = 1.92 × 10-10).DiscussionOur study demonstrated that an enriched case design can strengthen genetic signals, thus allowing detection of associations that would otherwise be missed in a traditional case-control study.

Original publication




Journal article


Alzheimer's & dementia : the journal of the Alzheimer's Association

Publication Date





441 - 452


Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.


Alzheimer's Disease Sequencing Project, Humans, Alzheimer Disease, Genetic Predisposition to Disease, Case-Control Studies, Age of Onset, Mutation, Missense, Aged, Aged, 80 and over, European Continental Ancestry Group, Hispanic Americans, Caspase 7, Genome-Wide Association Study