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P2‐141: CHR17Q21 H2 HAPLOTYPE STRATIFIED GWAS REVEALS DIFFERENTIAL ASSOCIATION FOR AD RISK VARIANTS
Author(s) -
Strickland Samantha L.,
Reddy Joseph S.,
Allen Mariet,
N'Songo Aurelie,
Burgess Jeremy D.,
Corda Morgane M.,
Ballard Travis,
Mukherjee Shubhabrata,
Boehme Kevin L.,
Crane Paul K.,
Kauwe John,
Ertekin-Taner Nilufer
Publication year - 2018
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.2018.06.827
Subject(s) - haplotype , linkage disequilibrium , genome wide association study , genetics , genetic association , biology , disease , genotype , medicine , single nucleotide polymorphism , gene
supervised admixture analyses usingWhiteswith European ancestry and African Yorubian from the HAPMAP project and Native Americans from the Human Diversity Genome Project. Global admixture individual proportions were then used to compute the kinship for each pair of the individuals. We then employed a logistic mixed effect model adjusting for sex, age as fixed effects and the kinship as randomeffect (Model 1).We also explored anAPOE-adjustedmodel (Model 2) and an interactionmodel (SNP*APOE –Model 3).Results: Global admixture analyses showed a 57% European, 34% African and 9% Native component. In addition to APOE, two loci reached genome-wide significance: in Model 1, a locus located on chromosome 2 lying within the MFSD2B gene, and in Model 2 a locus on chromosome 6 lying in the HLA region (p-value1⁄42.3*10-e8). Several LOAD-known genes were also enriched with significant variants, including ABCA7, MS4A cluster, SORL1. Conclusions: This is the largestGWASon subjects of CaribbeanHispanic ancestry phenotyped for LOAD to our knowledge. Several known-loci are being confirmed by our analyses, and two potentially novel loci are being reported. We are currently performing additional analyses and models and functional experiments to further validate our findings.