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Chunk #76 — Online Methods — Colocalization (coloc and SMR/HEIDI) analyses

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A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease.
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Colocalization analysis of genetic variants associated with AD and myeloid gene expression was performed using AAOS GWAS SNP and myeloid (monocyte and macrophage) eQTL datasets from Cardiogenics as inputs. Overlapping SNPs were retained within the hg19 region chr11:47100000-48100000 for the SPI1/CELF1 locus, chr11:59500000-60500000 for the MS4A locus, and chr1:169300000-170300000 for the SELL locus. Colocalization analysis of AD- and gene expression-associated SNPs was performed using the ‘coloc.abf’ function in the ‘coloc’ R package (v2.3-1). Default settings were used as prior probability of association: 1×10−4 for trait 1 (gene expression), 1×10−4 for trait 2 (AD) and 1×10−5 for both traits. SMR/HEIDI (v0.65) analysis was performed as described in Zhu et al.23 and the companion website (see URLs). The ADGC subset of the IGAP GWAS dataset was used to perform the LD calculations.