Overrepresentation of glutamate signaling in Alzheimer's disease: network-based pathway enrichment using meta-analysis of genome-wide association studies.

In particular, highly significant genome-wide associations signals were observed in the coding region of the translocase of the mitochondrial outer membrane gene (TOMM40: rs2075650, p = 8.54×10 −116 , OR = 4.48; rs157580, p = 9.6×10 −35 , OR = 0.51 and rs8106922, p = 1.17×10 −25 , OR = 0.57), upstream of the apolipoprotein C-I gene (APOC1: rs439401, p = 8.82×10 −29 , OR = 0.54), inside the poliovirus receptor related 2 isoform delta gene (PVRL2: rs6859, p = 7.87×10 −28 , OR = 1.7 and rs3852861 p = 5.32×10 −11 , OR = 0.64) and between TOMM40 and the APOE gene (rs405509, p = 2.29×10 −27 , OR = 0.57).

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Interestingly, among the top 25 associations detected, novel genome-wide marginally significant signals outside chromosome 19 were observed: in chromosome 12 (intergenic: rs249153, p = 4.38×10 −07 , OR = 1.41; intergenic: rs249166 and rs249167, both with p = 6.91×10 −07 and OR = 1.40) and in chromosome 5 (intergenic: rs13178362, p = 6.60×10 −07 , OR = 0.75), followed by trends inside the memb

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