Key result
A genome-wide association study using informed conditioning identified novel loci, including one downstream of SLC10A2, significantly associated with late-onset Alzheimer's disease in African Americans.
Case-Control (n=5,609)
An informed conditioning approach identified two novel genetic loci (COBL and SLC10A2) associated with late-onset Alzheimer's disease in African Americans.
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Hypothesis-generating for ancestry-specific Alzheimer's loci in African Americans; leaves open replication and clinical translation.
INTRODUCTION: African Americans' (AAs) late-onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power. METHODS: We conducted a genome-wide association study (GWAS) in AAs employing informed conditioning in 1825 LOAD cases and 3784 cognitively normal controls. We derived a posterior liability conditioned on age, sex, diabetes status, current smoking status, educational attainment, and affection status, with parameters informed by external prevalence information. We assessed association between the posterior liability and a genome-wide set of single-nucleotide polymorphisms (SNPs), controlling for APOE and ABCA7, identified previously in a LOAD GWAS of AAs. RESULTS: ), downstream of SLC10A2, obtained genome-wide significant evidence of association with the posterior liability. DISCUSSION: An informed conditioning approach can detect LOAD genetic associations in AAs not identified by traditional GWAS.
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Mez et al. (2016) conducted a case-control in Late-onset Alzheimer's disease (n=5,609). Single-nucleotide polymorphisms (SNPs) vs. Cognitively normal controls was evaluated on Association with posterior liability for late-onset Alzheimer's disease. A genome-wide association study using informed conditioning identified novel loci, including one downstream of SLC10A2, significantly associated with late-onset Alzheimer's disease in African Americans.
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