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Chunk #34 — ONLINE METHODS — Data acquisition, quality control, and normalization — Genotyping.

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Integrative transcriptome analyses of the aging brain implicate altered splicing in Alzheimer's disease susceptibility.
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DNA from ROS and MAP subjects was extracted from whole blood, lymphocytes or frozen post-mortem brain tissue and genotyped on the Affymetrix GeneChip 6.0 platform at the Broad Institute’s Center for Genotyping. Only self-declared non-Latino Caucasians were genotyped to minimize population heterogeneity. PLINK software52 was used to implement our QC pipeline. We applied standard QC measures for subjects (genotype success rate >95%, genotype-derived gender concordant with reported gender, excess inter/intra-heterozygosity) and for single nucleotide polymorphisms (SNPs) (HWE P > 0.001; MAF > 0.01, genotype call rate > 0.95; misshap test > 1×10−9) to these data. Subsequently, EIGENSTRAT53 was used to identify and remove population outliers using default parameters. Imputation was performed using Michigan Imputation Server with Minimac354 using Haplotype Reference Consortium (HRC version r1.1, 2016)55 panel consisting of 64,940 haplotypes of predominantly European ancestry. Imputation filtering of r2 > 0.3 was used for quality control. After QC, 450 individuals and 8,383,662 genotyped or imputed markers were used for sQTL analysis.