TREM2 variants in Alzheimer's disease.

来自掌桥科研

喜欢 0

阅读量：

409

作者：

R Guerreiro，A Wojtas，J Bras，M Carrasquillo，J Hardy

展开

摘要：

BACKGROUND;Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia.METHODS;We used genome, exome, and Sanger sequencing to analyze the genetic variability in TREM2 in a series of 1092 patients with Alzheimer's disease and 1107 controls (the discovery set). We then performed a meta-analysis on imputed data for the TREM2 variant rs75932628 (predicted to cause a R47H substitution) from three genomewide association studies of Alzheimer's disease and tested for the association of the variant with disease. We genotyped the R47H variant in an additional 1887 cases and 4061 controls. We then assayed the expression of TREM2 across different regions of the human brain and identified genes that are differentially expressed in a mouse model of Alzheimer's disease and in control mice.RESULTS;We found significantly more variants in exon 2 of TREM2 in patients with Alzheimer's disease than in controls in the discovery set (P = 0.02). There were 22 variant alleles in 1092 patients with Alzheimer's disease and 5 variant alleles in 1107 controls (PCONCLUSIONS;Heterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer's disease. (Funded by Alzheimer's Research UK and others.)

展开

关键词：

GENOME-WIDE ASSOCIATION DNA-SEQUENCING DATA MISSENSE MUTATIONS IDENTIFIES VARIANTS COMMON VARIANTS TRANSGENIC MICE GENE MICROGLIA FRAMEWORK CD2AP