RT Journal Article
SR Electronic
T1 African American exome sequencing identifies potential risk variants at Alzheimer disease loci
JF Neurology Genetics
JO Neurol Genet
FD Lippincott Williams & Wilkins
SP e141
DO 10.1212/NXG.0000000000000141
VO 3
IS 2
A1 Aurelie N'Songo
A1 Minerva M. Carrasquillo
A1 Xue Wang
A1 Jeremy D. Burgess
A1 Thuy Nguyen
A1 Yan W. Asmann
A1 Daniel J. Serie
A1 Steven G. Younkin
A1 Mariet Allen
A1 Otto Pedraza
A1 Ranjan Duara
A1 Maria T. Greig Custo
A1 Neill R. Graff-Radford
A1 Nilüfer Ertekin-Taner
YR 2017
UL http://ng.neurology.org/content/3/2/e141.abstract
AB Objective: In African Americans, we sought to systematically identify coding Alzheimer disease (AD) risk variants at the previously reported AD genome-wide association study (GWAS) loci genes.Methods: We identified coding variants within genes at the 20 published AD GWAS loci by whole-exome sequencing of 238 African American participants, validated these in 300 additional participants, and tested their association with AD risk in the combined cohort of 538 and with memory endophenotypes in 319 participants.Results: Two ABCA7 missense variants (rs3764647 and rs3752239) demonstrated significant association with AD risk. Variants in MS4A6A, PTK2B, and ZCWPW1 showed significant gene-based association. In addition, coding variants in ZCWPW1 (rs6465770) and NME8 (rs10250905 and rs62001869) showed association with memory endophenotypes.Conclusions: Our findings support a role for ABCA7 missense variants in conferring AD risk in African Americans, highlight allelic heterogeneity at this locus, suggest the presence of AD-risk variants in MS4A6A, PTK2B, and ZCWPW1, nominate additional variants that may modulate cognition, and importantly provide a thorough screen of coding variants at AD GWAS loci that can guide future studies in this population.AD=Alzheimer disease; DR=delayed recall; GWAS=genome-wide association study; IGAP=The International Genomics of Alzheimer's Project; IR=immediate recall; LD=linkage disequilibrium; LM=Logical Memory; LOAD=late-onset Alzheimer disease; MAF=minor allele frequency; OR=odds ratio; PR=percent retention; QC=quality control; SNP=single nucleotide polymorphism; VR=Visual Reproduction; WES=whole-exome sequencing