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Details of Genomewide Association Results, Protocol, Statistical Analysis, and Additional References (Harlaar et al., 2014)

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posted on 01.02.2014, 00:00 by Nicole Harlaar, Emma L. Meaburn, Marianna E. Hayiou-Thomas, Oliver S. P. Davis, Sophia Docherty, Ken B. Hanscombe, Claire M. A. Haworth, Thomas S. Price, Maciej Trzaskowski, Philip S. Dale, Robert Plomin
Purpose Researchers have previously shown that individual differences in measures of receptive language ability at age 12 are highly heritable. In the current study, the authors attempted to identify some of the genes responsible for the heritability of receptive language ability using a genome-wide association approach.
Method The authors administered 4 Internet-based measures of receptive language (vocabulary, semantics, syntax, and pragmatics) to a sample of 2,329 twelve-year-olds for whom DNA and genome-wide genotyping were available. Nearly 700,000 single-nucleotide polymorphisms (SNPs) and 1 million imputed SNPs were included in a genome-wide association analysis of receptive language composite scores.
Results No SNP associations met the demanding criterion of genome-wide significance that corrects for multiple testing across the genome ( p < 5 × 10−8). The strongest SNP association did not replicate in an additional sample of 2,639 twelve-year-olds.
Conclusions These results indicate that individual differences in receptive language ability in the general population do not reflect common genetic variants that account for more than 3% of the phenotypic variance. The search for genetic variants associated with language skill will require larger samples and additional methods to identify and functionally characterize the full spectrum of risk variants.

Funding

We gratefully acknowledge the ongoing contribution of the parents and children in the Twins Early Development Study (TEDS). TEDS is supported by a program grant [G0901245; and previously G0500079] from the U.K. Medical Research Council (MRC), with additional support from the US National Institutes of Health [HD044454; HD059215]. R.P. is supported by a Medical Research Council Research Professorship award [G19/2] and a European Advanced Investigator award [295366]; O.S.P.D. is supported by a Sir Henry Wellcome Fellowship from the Wellcome Trust [WT088984]; C.M.A.H. is supported by a research fellowship from the British Academy. Genome-wide genotyping was made possible by grants from the Wellcome Trust Case Control Consortium 2 project [085475/B/08/Z; 085475/Z/08/Z]; see below for membership of WTCCC2 and member affiliations. WTCCC2 membership is as follows: Management Committee: Peter Donnelly (Chair), 1,2 Ines Barroso (Deputy Chair), 3 Jenefer M. Blackwell, 4,5 Elvira Bramon, 6 Matthew A. Brown, 7 Juan P. Casas, 8 Aiden Corvin, 9 Panos Deloukas, 3 Audrey Duncanson, 10 Janusz Jankowski, 11 Hugh S. Markus, 12 Christopher G. Mathew, 13 Colin N. A. Palmer, 14 Robert Plomin, 15 Anna Rautanen, 1 Stephen J. Sawcer, 16 Richard C. Trembath, 13 Ananth C. Viswanathan, 17 and Nicholas W. Wood. 18 Data and Analysis Group: Chris C. A. Spencer, 1 Gavin Band, 1 Céline Bellenguez, 1 Colin Freeman, 1 Garrett Hellenthal, 1 Eleni Giannoulatou, 1 Matti Pirinen, 1 Richard Pearson, 1 Amy Strange, 1 Zhan Su, 1 Damjan Vukcevic, 1 and Peter Donnelly. 1,2 DNA, Genotyping, Data Quality Control, and Informatics Group: Cordelia Langford, 3 Sarah E. Hunt, 3 Sarah Edkins, 3 Rhian Gwilliam, 3 Hannah Blackburn, 3 Suzannah J. Bumpstead, 3 Serge Dronov, 3 Matthew Gillman, 3 Emma Gray, 3 Naomi Hammond, 3 Alagurevathi Jayakumar, 3 Owen T. McCann, 3 Jennifer Liddle, 3 Simon C. Potter, 3 Radhi Ravindrarajah, 3 Michelle Ricketts, 3 Matthew Waller, 3 Paul Weston, 3 Sara Widaa, 3 Pamela Whittaker, 3 Ines B

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