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Chunk #14 — Method — Measures — Genetic variables-PRS

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Polygenic signal for symptom dimensions and cognitive performance in patients with chronic schizophrenia.
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We constructed PRS using the methods suggested by the International Schizophrenia Consortium (Purcell et al., 2009) using the ‘fastscore’ option in PRSice software package (Euesden et al., 2015). To curate a most informative SNP list for PRS calculations the SNPs are first filtered to address linkage disequilibrium (LD). We used the clump option to address LD by applying thresholds of r2 ≥ 0.1 and distance of 500 kb. Since SNPs in the major histocompatibility complex region of the genome have long range LD, we also removed SNPs in the MHC region (26–33 Mb) prior to constructing PRS. PRS was calculated on an a priori set of significance thresholds (PT = 5e-08, 1e-07, 1e-06, 1e-05, 1e-04, 1e-03, 0.01, 0.05, 0.1,0.2,0.3,0.4 and 0.5) to identify the best fit PRS that was most predictive of an association. Multiple comparisons were addressed by applying 106 permutations.