Quantitative trait locus association scan of early reading disability and ability using pooled DNA and 100K SNP microarrays in a sample of 5760 children.

Full 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.

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Author information

Author/s: Meaburn, E L (EL); Harlaar, N (N); Craig, I W (IW); Schalkwyk, L C (LC); Plomin, R (R);

Affiliation: Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College, London, UK. e.meaburn(-atsign-)iop.kcl.ac.uk

Grants: G0500079 (Agency:United Kingdom Medical Research Council) ; HD49861 (Agency:United States NICHD)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Twin Study

Journal: Molecular psychiatry (Mol Psychiatry), published in England. (Language: eng)

Reference: 2008-Jul; vol 13 (issue 7) : pp 729-40

Dates: Created 2008/06/18; Completed 2008/08/13;

PMID: 17684495, status: MEDLINE (last retrieval date: 11/6/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Child
Child Development
DNA - genetics
Dyslexia - genetics
Gene Frequency

Humans
Oligonucleotide Array Sequence Analysis
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Reading

Associated Chemicals: DNA (9007-49-2)

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