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Chunk #14 — Methods — Statistical Analysis

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Mapping of gene expression reveals CYP27A1 as a susceptibility gene for sporadic ALS.
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For the eQTL analyses, SNP genotypes coded as an additive genetic model were tested for association with gene expression by linear regression using disease status, age, gender, surrogate variables (18 in the discovery set and 19 in the replication) and riluzole use as covariates. Cis eQTLs were defined as SNPs modulating transcript expression levels within a region of 1Mb surrounding a probe’s genomic midpoint [26]. False-positive cis effects may, however, occur due to SNPs that are located within a transcript probe or that are in linkage disequilibrium (LD) with SNPs mapping within a transcript probe [33]. We used the Broad Institute SNAP tool v2.2 [34] to determine pairwise LD between cis effect SNPs and SNPs mapping to a transcript probe in either of the HapMap phase III release 2 or 1000 Genomes Pilot 1 CEU panels. 21,863 SNP-transcript combinations (pairwise LD threshold r2 >0.2) were excluded from analysis. Similarly, we removed 24,170 SNP-transcript combinations with an InDel overlapping with a transcript probe, according to the Database of Genomic Variants (version 10, November 2010) [35]. There were 3,541,781 possible SNP-transcript combinations