Computational protocol: PCSK6 is associated with handedness in individuals with dyslexia

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Protocol publication

[…] We used IMPUTE [v2.0.5 for autosomes, () and v1.0.0 for the X chromosome, ()] to estimate the genotypes of SNPs not directly genotyped on the Illumina 550k platform. This involved combining information from (i) the directly genotyped SNPs, (ii) a densely genotyped reference panel (60 CEPH founders from HapMap Phase II, build 35) and (iii) a fine-scale recombination map, to infer the missing genotypes. Imputed SNPs were filtered out if they had an MAF < 0.05 or proper info <0.5, allowing for us to test a further 1 709 209 SNPs for association. [...] Directly genotyped and imputed SNPs were tested for association with the quantitative measure PegQ under an additive model using SNPTEST (v1.1.4, www.stats.ox.ac.uk/~marchini/software/gwas/snptest.html date last accessed 12/11/10) simultaneously specifying sex and age as covariates. For the X chromosome, analysis in stage 1 was conducted by running the association test separately for the two sexes in SNPTEST and combined the results using GWAMA [v1.4, ()], which performs fixed effects meta-analysis using inverse-variance weighting of the parameter estimates. The results for the three stages were then meta-analyzed using GWAMA (). The values of PegQ were standardized in all stages separately to give a mean of 0, and a SD of 1. For the two SNPs genotyped in ALSPAC in the general population, the absolute value of the standardized PegQ score was also run as a quantitative phenotype.To rule out any underlying confounding effects, we tested rs11855415 and rs9806256 for association with measures of hand motor skill, IQ and reading ability (CCI, CCN, OLSON, READ, SPELL, SPOON, defined in Supplementary Material), in each of the three stages as well as in the general population sample whenever data were available, and found no significant association (Supplementary Material, Table S2). […]

Pipeline specifications

Software tools IMPUTE, SNPTEST, GWAMA
Application GWAS
Organisms Homo sapiens