Meta-analysis of linkage studies for Alzheimer's disease—A web resource

Abstract 

Familial late-onset Alzheimer's disease (LOAD) shows high heritability. However, with the exception of ApoE, no well-replicated susceptibility genes have been identified to date. Several genome-wide linkage studies have nominated potential susceptibility loci but results are inconsistent, with individual scans showing few significant LOD scores. We have pooled linkage results from five independent genome scans and used the genome search meta-analysis (GSMA) method to analyse these data. The combined sample results in 2206 affected individuals and 785 families from Caucasian and Caribbean Hispanic ethnicities. The Caucasian samples included subjects from the US, the Netherlands and Sweden. Genome-wide suggestive evidence for linkage was observed on chromosomes 1p13.3-q31.1, 7pter-p21.1 and 8p22-p21.1 in the weighted GSMA analysis. The chromosome 8p region achieved the lowest summed rank p-value of 0.001. We also identified seven loci with nominally significant evidence for linkage to 3q12.3-q22.1, 6p21.1-q15, 7p14.1-q21.11, 17q24.3-qter and 19p13.3-qter. The GSMA finding suggests that these loci may harbour susceptibility genes for LOAD. We have also developed a web resource (http://alzres.iop.kcl.ac.uk/) to present additional GSMA analyses with different study selection criteria, facilitate the reanalysis of genome-wide linkage data and provide open access to the GSMA data.

Keywords: Alzheimer's disease, Late-onset Alzheimer's disease, Linkage (genetics), Meta-analysis, Genome search meta-analysis