First genome-wide association study on anxiety-related behaviours in childhood.

<h4>Background</h4>Twin studies have shown that anxiety in a general population sample of children involves both domain-general and trait-specific genetic effects. For this reason, in an attempt to identify genes responsible for these effects, we investigated domain-general and trait-spe...

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Autores principales:	Maciej Trzaskowski, Thalia C Eley, Oliver S P Davis, Sophia J Doherty, Ken B Hanscombe, Emma L Meaburn, Claire M A Haworth, Thomas Price, Robert Plomin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5b89c2f72f2142779a29c558aafccb58
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spelling	oai:doaj.org-article:5b89c2f72f2142779a29c558aafccb582021-11-18T07:51:08ZFirst genome-wide association study on anxiety-related behaviours in childhood.1932-620310.1371/journal.pone.0058676https://doaj.org/article/5b89c2f72f2142779a29c558aafccb582013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23565138/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Twin studies have shown that anxiety in a general population sample of children involves both domain-general and trait-specific genetic effects. For this reason, in an attempt to identify genes responsible for these effects, we investigated domain-general and trait-specific genetic associations in the first genome-wide association (GWA) study on anxiety-related behaviours (ARBs) in childhood.<h4>Methods</h4>The sample included 2810 7-year-olds drawn from the Twins Early Development Study (TEDS) with data available for parent-rated anxiety and genome-wide DNA markers. The measure was the Anxiety-Related Behaviours Questionnaire (ARBQ), which assesses four anxiety traits and also yields a general anxiety composite. Affymetrix GeneChip 6.0 DNA arrays were used to genotype nearly 700,000 single-nucleotide polymorphisms (SNPs), and IMPUTE v2 was used to impute more than 1 million SNPs. Several GWA associations from this discovery sample were followed up in another TEDS sample of 4804 children. In addition, Genome-wide Complex Trait Analysis (GCTA) was used on the discovery sample, to estimate the total amount of variance in ARBs that can be accounted for by SNPs on the array.<h4>Results</h4>No SNP associations met the demanding criterion of genome-wide significance that corrects for multiple testing across the genome (p<5×10(-8)). Attempts to replicate the top associations did not yield significant results. In contrast to the substantial twin study estimates of heritability which ranged from 0.50 (0.03) to 0.61 (0.01), the GCTA estimates of phenotypic variance accounted for by the SNPs were much lower 0.01 (0.11) to 0.19 (0.12).<h4>Conclusions</h4>Taken together, these GWAS and GCTA results suggest that anxiety--similar to height, weight and intelligence--is affected by many genetic variants of small effect, but unlike these other prototypical polygenic traits, genetic influence on anxiety is not well tagged by common SNPs.Maciej TrzaskowskiThalia C EleyOliver S P DavisSophia J DohertyKen B HanscombeEmma L MeaburnClaire M A HaworthThomas PriceRobert PlominPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e58676 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maciej Trzaskowski Thalia C Eley Oliver S P Davis Sophia J Doherty Ken B Hanscombe Emma L Meaburn Claire M A Haworth Thomas Price Robert Plomin First genome-wide association study on anxiety-related behaviours in childhood.
description	<h4>Background</h4>Twin studies have shown that anxiety in a general population sample of children involves both domain-general and trait-specific genetic effects. For this reason, in an attempt to identify genes responsible for these effects, we investigated domain-general and trait-specific genetic associations in the first genome-wide association (GWA) study on anxiety-related behaviours (ARBs) in childhood.<h4>Methods</h4>The sample included 2810 7-year-olds drawn from the Twins Early Development Study (TEDS) with data available for parent-rated anxiety and genome-wide DNA markers. The measure was the Anxiety-Related Behaviours Questionnaire (ARBQ), which assesses four anxiety traits and also yields a general anxiety composite. Affymetrix GeneChip 6.0 DNA arrays were used to genotype nearly 700,000 single-nucleotide polymorphisms (SNPs), and IMPUTE v2 was used to impute more than 1 million SNPs. Several GWA associations from this discovery sample were followed up in another TEDS sample of 4804 children. In addition, Genome-wide Complex Trait Analysis (GCTA) was used on the discovery sample, to estimate the total amount of variance in ARBs that can be accounted for by SNPs on the array.<h4>Results</h4>No SNP associations met the demanding criterion of genome-wide significance that corrects for multiple testing across the genome (p<5×10(-8)). Attempts to replicate the top associations did not yield significant results. In contrast to the substantial twin study estimates of heritability which ranged from 0.50 (0.03) to 0.61 (0.01), the GCTA estimates of phenotypic variance accounted for by the SNPs were much lower 0.01 (0.11) to 0.19 (0.12).<h4>Conclusions</h4>Taken together, these GWAS and GCTA results suggest that anxiety--similar to height, weight and intelligence--is affected by many genetic variants of small effect, but unlike these other prototypical polygenic traits, genetic influence on anxiety is not well tagged by common SNPs.
format	article
author	Maciej Trzaskowski Thalia C Eley Oliver S P Davis Sophia J Doherty Ken B Hanscombe Emma L Meaburn Claire M A Haworth Thomas Price Robert Plomin
author_facet	Maciej Trzaskowski Thalia C Eley Oliver S P Davis Sophia J Doherty Ken B Hanscombe Emma L Meaburn Claire M A Haworth Thomas Price Robert Plomin
author_sort	Maciej Trzaskowski
title	First genome-wide association study on anxiety-related behaviours in childhood.
title_short	First genome-wide association study on anxiety-related behaviours in childhood.
title_full	First genome-wide association study on anxiety-related behaviours in childhood.
title_fullStr	First genome-wide association study on anxiety-related behaviours in childhood.
title_full_unstemmed	First genome-wide association study on anxiety-related behaviours in childhood.
title_sort	first genome-wide association study on anxiety-related behaviours in childhood.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/5b89c2f72f2142779a29c558aafccb58
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First genome-wide association study on anxiety-related behaviours in childhood.

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