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Chunk #43 — Review

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Genome-wide association studies in ADHD.
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Of the 304 controls only 54 were screened for psychiatric disorders prior to inclusion. Genotyping was on the Affymetrix GeneChip Human Mapping 500K sets. Importantly, instead of genotyping individual samples, pools were constructed of the 343 cases and 304 controls, respectively. For each pool nine technical replicates were analyzed. After data cleaning the authors ended up with allele frequencies for 504,219 SNPs, of which the autosomal SNPs were ranked based on the mean of rankings performed using ANOVA, rank sums and silhouette scores. Whereas the other ADHD GWAS reports relied strictly on statistical rankings to describe their results, Lesch and coworkers used additional criteria for further prioritization of SNPs for follow up, one being localization within or near genes (±100 kb flanking region), a second being presence in clusters of at least three SNPs located in regions of genes, a third being the comparison with a family-based association study performed in a dataset from a recently published linkage paper by the same group, or being present in a suggestive linkage region from this analysis in adult ADHD patients (Romanos et al. 2008). In addition, expression in brain, as well as earlier findings suggesting involvement in complex traits and neuropsychiatric disorders