Wellcome Trust Case Control Consortium 2 (Including: Viding, Essi, Price, Tom S., Jaffee, Sara R., Trzaskowski, Maciej, Davis, Oliver S. P., Meaburn, Emma L., Haworth, Claire M. A. and Plomin, Robert). (2013) Genetics of callous-unemotional behavior in children. PLoS One, Volume 8 (Number 7). Article number e65789. doi:10.1371/annotation/0b16418f-ceb5-41b2-be2a-a20f0c56f9a6 ISSN 1932-6203.

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Abstract

Callous-unemotional behavior (CU) is currently under consideration as a subtyping index for conduct disorder diagnosis. Twin studies routinely estimate the heritability of CU as greater than 50%. It is now possible to estimate genetic influence using DNA alone from samples of unrelated individuals, not relying on the assumptions of the twin method. Here we use this new DNA method (implemented in a software package called Genome-wide Complex Trait Analysis, GCTA) for the first time to estimate genetic influence on CU. We also report the first genome-wide association (GWA) study of CU as a quantitative trait. We compare these DNA results to those from twin analyses using the same measure and the same community sample of 2,930 children rated by their teachers at ages 7, 9 and 12. GCTA estimates of heritability were near zero, even though twin analysis of CU in this sample confirmed the high heritability of CU reported in the literature, and even though GCTA estimates of heritability were substantial for cognitive and anthropological traits in this sample. No significant associations were found in GWA analysis, which, like GCTA, only detects additive effects of common DNA variants. The phrase 'missing heritability' was coined to refer to the gap between variance associated with DNA variants identified in GWA studies versus twin study heritability. However, GCTA heritability, not twin study heritability, is the ceiling for GWA studies because both GCTA and GWA are limited to the overall additive effects of common DNA variants, whereas twin studies are not. This GCTA ceiling is very low for CU in our study, despite its high twin study heritability estimate. The gap between GCTA and twin study heritabilities will make it challenging to identify genes responsible for the heritability of CU.

Item Type:	Journal Article
Subjects:	R Medicine > RJ Pediatrics
Divisions:	Faculty of Science, Engineering and Medicine > Science > Psychology
Library of Congress Subject Headings (LCSH):	Behavior disorders in children, Behavior genetics
Journal or Publication Title:	PLoS One
Publisher:	Public Library of Science
ISSN:	1932-6203
Official Date:	9 July 2013
Dates:	Date Event 9 July 2013 Published 29 April 2013 Accepted 21 January 2013 Submitted
Volume:	Volume 8
Number:	Number 7
Number of Pages:	9
Article Number:	Article number e65789
DOI:	10.1371/annotation/0b16418f-ceb5-41b2-be2a-a20f0c56f9a6
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	28 December 2015
Date of first compliant Open Access:	28 December 2015
Funder:	Medical Research Council (Great Britain) (MRC), National Institutes of Health (U.S.) (NIH), European Research Council (ERC), Wellcome Trust (London, England), British Academy (BA)
Grant number:	G0500079 (MRC), HD044454 (NIH), HD046167 (NIH), G19/2 (MRC), 295366 (ERC), WT088984 (WT), 085475/B/08/Z (WT), 085475/Z/08/Z (WT)

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