Genome-wide pathway analysis implicates intracellular transmembrane protein transport in Alzheimer disease.

Mun-Gwan Hong, Andrey Alexeyenko, Jean-Charles Lambert, Philippe Amouyel, Jonathan A Prince

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Journal of human genetics 2010 Oct

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We developed and implemented software for the analysis of genome-wide association studies in the context of biological pathway enrichment and have here applied our algorithm to the study of Alzheimer disease (AD). Using genome-wide association data in a large French population, we observed a highly significant enrichment of genes involved in intracellular protein transmembrane transport, including several mitochondrial proteins and nucleoporins. An intriguing aspect of these findings is the implication that TOMM40, the channel-forming subunit of the translocase of the mitochondrial outer membrane complex, and a gene generally considered to be indiscernible from APOE because of linkage disequilibrium, may itself contribute to Alzheimer pathology. Results provide an indication that protein trafficking, in particular across the nuclear and mitochondrial membranes, may contribute to risk for AD.

Citation

Mun-Gwan Hong, Andrey Alexeyenko, Jean-Charles Lambert, Philippe Amouyel, Jonathan A Prince. Genome-wide pathway analysis implicates intracellular transmembrane protein transport in Alzheimer disease. Journal of human genetics. 2010 Oct;55(10):707-9