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Genome-wide association study of receptive language ability of 12-year-olds.

Harlaar N, Meaburn EL, Hayiou-Thomas ME, Wellcome Trust Case Control ConsortiumDavis OS, Docherty S, Hanscombe KB, Haworth CM, Price TS, Trzaskowski M, Dale PS, Plomin R - J. Speech Lang. Hear. Res. (2014)

Bottom Line: The strongest SNP association did not replicate in an additional sample of 2,639 twelve-year-olds.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.

View Article: PubMed Central - PubMed

ABSTRACT

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.

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Manhattan plot for general language ability at age 12. Negative log base 10 p values from a mixed-effects model likelihoood ratio test are plotted against genomic position.
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Figure 3: Manhattan plot for general language ability at age 12. Negative log base 10 p values from a mixed-effects model likelihoood ratio test are plotted against genomic position.

Mentions: An alternative approach to visualizing these results is to use a Manhattan plot, shown in Figure 3. Each point represents a different SNP, laid out across the 22 human autosomes on the x-axis. The negative log base 10 p values are plotted on the y-axis. Evidence for a significant association would be indicated if we were able to detect a cluster of SNPs that form a “tower” (resembling a Manhattan skyscraper), the result of nearby SNPs being in LD with one another and thus all marking the same association signal. In the discovery sample, none of the SNPs reached the conventional genome-wide significance threshold of p < 5 × 10–8. One SNP (rs12474600) on chromosome 2 showed an association just below this threshold (p = 4.57 × 10–7, B = –0.24, SE = 0.05, n = 2329; the solid red line in Figure 3). Clusters of low p values were also observed on chromosomes 10 and 19. The 114 strongest associations (p ≤ 1 × 104; the solid blue line in Figure 3) are detailed in Supplementary Table 2.


Genome-wide association study of receptive language ability of 12-year-olds.

Harlaar N, Meaburn EL, Hayiou-Thomas ME, Wellcome Trust Case Control ConsortiumDavis OS, Docherty S, Hanscombe KB, Haworth CM, Price TS, Trzaskowski M, Dale PS, Plomin R - J. Speech Lang. Hear. Res. (2014)

Manhattan plot for general language ability at age 12. Negative log base 10 p values from a mixed-effects model likelihoood ratio test are plotted against genomic position.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3974169&req=5

Figure 3: Manhattan plot for general language ability at age 12. Negative log base 10 p values from a mixed-effects model likelihoood ratio test are plotted against genomic position.
Mentions: An alternative approach to visualizing these results is to use a Manhattan plot, shown in Figure 3. Each point represents a different SNP, laid out across the 22 human autosomes on the x-axis. The negative log base 10 p values are plotted on the y-axis. Evidence for a significant association would be indicated if we were able to detect a cluster of SNPs that form a “tower” (resembling a Manhattan skyscraper), the result of nearby SNPs being in LD with one another and thus all marking the same association signal. In the discovery sample, none of the SNPs reached the conventional genome-wide significance threshold of p < 5 × 10–8. One SNP (rs12474600) on chromosome 2 showed an association just below this threshold (p = 4.57 × 10–7, B = –0.24, SE = 0.05, n = 2329; the solid red line in Figure 3). Clusters of low p values were also observed on chromosomes 10 and 19. The 114 strongest associations (p ≤ 1 × 104; the solid blue line in Figure 3) are detailed in Supplementary Table 2.

Bottom Line: The strongest SNP association did not replicate in an additional sample of 2,639 twelve-year-olds.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.

View Article: PubMed Central - PubMed

ABSTRACT

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.

Show MeSH