Abstract
To follow-up loci discovered by the International Genomics of Alzheimer's Disease Project, we attempted independent replication of 19 single nucleotide polymorphisms (SNPs) in a large Spanish sample (Fundació ACE data set; 1808 patients and 2564 controls). Our results corroborate association with four SNPs located in the genes INPP5D, MEF2C, ZCWPW1 and FERMT2, respectively. Of these, ZCWPW1 was the only SNP to withstand correction for multiple testing (P=0.000655). Furthermore, we identify TRIP4 (rs74615166) as a novel genome-wide significant locus for Alzheimer's disease risk (odds ratio=1.31; confidence interval 95% (1.19–1.44); P=9.74 × 10−9).
Highlights
Alzheimer’s disease (AD) is a complex multifactorial neuropsychiatric disorder whose etiology involves both environmental and genetic factors
The analysis identified 13 suggestive loci
These findings may serve as the starting point for novel discoveries in future AD genomics studies
Summary
Alzheimer’s disease (AD) is a complex multifactorial neuropsychiatric disorder whose etiology involves both environmental and genetic factors. Subsequent meta-analyses of genome-wide association studies identified further genetic risk loci. Four of the 11 genome-wide significant loci in the IGAP analyses reached significance in stage 1 (rs8093731 DSG2; rs28834970 PTK2B; rs11218343 SORL1; rs10498633 SLC24A4).
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