01913nas a2200229 4500008004100000022001400041245008600055210006900141260001300210300001100223490000700234520117200241653001501413653002201428653001001450653003801460653003401498653001101532653003601543110006801579856003601647 2015 eng d a1552-527900aConvergent genetic and expression data implicate immunity in Alzheimer's disease.0 aConvergent genetic and expression data implicate immunity in Alz c2015 Jun a658-710 v113 a

BACKGROUND: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis.

METHODS: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain.

RESULTS: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10(-11)), cholesterol transport (P = 2.96 × 10(-9)), and proteasome-ubiquitin activity (P = 1.34 × 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05).

CONCLUSIONS: The immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.

10aAlgorithms10aAlzheimer Disease10aBrain10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aHumans10aPolymorphism, Single Nucleotide1 aInternational Genomics of Alzheimer's Disease Consortium (IGAP) uhttps://chs-nhlbi.org/node/7018