Quantitative trait locus association scan of early reading disability and ability using pooled DNA and 100K SNP microarrays in a sample of 5760 children
Meaburn, Emma L. and Harlaar, N. and Craig, I.W. and Schalkwyk, L.C. and Plomin, R. (2008) Quantitative trait locus association scan of early reading disability and ability using pooled DNA and 100K SNP microarrays in a sample of 5760 children. Molecular Psychiatry 13 (7), pp. 729-40. ISSN 1359-4184.
Abstract
Quantitative genetic research suggests that reading disability is the quantitative extreme of the same genetic and environmental factors responsible for normal variation in reading ability. This finding warrants a quantitative trait locus (QTL) strategy that compares low versus high extremes of the normal distribution of reading in the search for QTLs associated with variation throughout the distribution. A low reading ability group (N=755) and a high reading group (N=747) were selected from a representative UK sample of 7-year-olds assessed on two measures of reading that we have shown to be highly heritable and highly genetically correlated. The low and high reading ability groups were each divided into 10 independent DNA pools and the 20 pools were assayed on 100 K single nucleotide polymorphism (SNP) microarrays to screen for the largest allele frequency differences between the low and high reading ability groups. Seventy five of these nominated SNPs were individually genotyped in an independent sample of low (N=452) and high (N=452) reading ability children selected from a second sample of 4258 7-year-olds. Nine of the seventy-five SNPs were nominally significant (P<0.05) in the predicted direction. These 9 SNPs and 14 other SNPs showing low versus high allele frequency differences in the predicted direction were genotyped in the rest of the second sample to test the QTL hypothesis. Ten SNPs yielded nominally significant linear associations in the expected direction across the distribution of reading ability. However, none of these SNP associations accounted for more than 0.5% of the variance of reading ability, despite 99% power to detect them. We conclude that QTL effect sizes, even for highly heritable common disorders and quantitative traits such as early reading disability and ability, might be much smaller than previously considered.
Metadata
| Item Type: | Article |
|---|---|
| Keyword(s) / Subject(s): | dyslexia, learning disability, DNA pooling, quantitative trait, allelic association, twins |
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Psychological Sciences |
| Research Centres and Institutes: | Educational Neuroscience, Centre for, Brain and Cognitive Development, Centre for (CBCD) |
| Depositing User: | Emma Meaburn |
| Date Deposited: | 15 May 2013 08:41 |
| Last Modified: | 02 Aug 2023 17:03 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/6753 |
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