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O4–06–06: Vascular disease, vascular risk factors and risk of late‐onset Alzheimer's disease: Mendelian randomization analyses in the combined ADGC dataset
Author(s) -
Mukherjee Shubhabrata,
Walter Stefan,
Yang Hyuna,
Jarvik Gail,
Crosslin David,
Lee SuIn,
Fardo David,
Green Robert,
Sherva Richard,
Walker Rod,
Larson Eric,
Schellenberg Gerard,
Glymour Maria,
Crane Paul
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.04.370
Subject(s) - mendelian randomization , blood pressure , medicine , genome wide association study , linkage disequilibrium , pulse pressure , type 2 diabetes , glycated hemoglobin , single nucleotide polymorphism , myocardial infarction , diabetes mellitus , cardiology , endocrinology , biology , genetics , genotype , genetic variants , gene
<2x10 were evaluated in Stage 2, and evidence of association was confirmed for one SORL1 SNP (rs3781834, P1⁄47.33x10 in the combined sample). Subsequent analysis combining results for several SORL1 SNPs in all datasets revealed genomewide significance with rs11218343 (P1⁄41.77x10) and rs3781834 (P1⁄41.04x10). SNPs in previously established AD loci in Caucasians showed strong evidence of association in Japanese including rs3851179 near PICALM (P1⁄41.71x10) and rs744373 near BIN1 (P1⁄41.39x10). The associated allele for each of these SNPs was the same as in Caucasians. Conclusions: These data demonstrate for the first time genome-wide significance of LOAD with SORL1 and confirm the role of other known loci for LOAD in Japanese people. Our study highlights the importance of examining associations in multiple ethnic populations.