Most genetic risk for autism resides with common variation

A key component of genetic architecture is the allelic spectrum influencing trait variability. For autism spectrum disorder (henceforth autism) the nature of its allelic spectrum is uncertain. Individual risk genes have been identified from rare variation, especially de novo mutations1–8. From this...

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Main Authors:	Gaugler, Trent, Klei, Lambertus, Sanders, Stephan J., Bodea, Corneliu A., Goldberg, Arthur P., Lee, Ann B., Mahajan, Milind, Manaa, Dina, Pawitan, Yudi, Reichert, Jennifer, Ripke, Stephan, Sandin, Sven, Sklar, Pamela, Svantesson, Oscar, Reichenberg, Abraham, Hultman, Christina M., Devlin, Bernie, Roeder, Kathryn, Buxbaum, Joseph D.
Format:	Online
Language:	English
Published:	2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137411/

id	pubmed-4137411
recordtype	oai_dc
spelling	pubmed-41374112015-02-01 Most genetic risk for autism resides with common variation Gaugler, Trent Klei, Lambertus Sanders, Stephan J. Bodea, Corneliu A. Goldberg, Arthur P. Lee, Ann B. Mahajan, Milind Manaa, Dina Pawitan, Yudi Reichert, Jennifer Ripke, Stephan Sandin, Sven Sklar, Pamela Svantesson, Oscar Reichenberg, Abraham Hultman, Christina M. Devlin, Bernie Roeder, Kathryn Buxbaum, Joseph D. Article A key component of genetic architecture is the allelic spectrum influencing trait variability. For autism spectrum disorder (henceforth autism) the nature of its allelic spectrum is uncertain. Individual risk genes have been identified from rare variation, especially de novo mutations1–8. From this evidence one might conclude that rare variation dominates its allelic spectrum, yet recent studies show that common variation, individually of small effect, has substantial impact en masse9,10. At issue is how much of an impact relative to rare variation. Using a unique epidemiological sample from Sweden, novel methods that distinguish total narrow-sense heritability from that due to common variation, and by synthesizing results from other studies, we reach several conclusions about autism’s genetic architecture: its narrow-sense heritability is ≈54% and most traces to common variation; rare de novo mutations contribute substantially to individuals’ liability; still their contribution to variance in liability, 2.6%, is modest compared to heritable variation. 2014-07-20 2014-08 /pmc/articles/PMC4137411/ /pubmed/25038753 http://dx.doi.org/10.1038/ng.3039 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Gaugler, Trent Klei, Lambertus Sanders, Stephan J. Bodea, Corneliu A. Goldberg, Arthur P. Lee, Ann B. Mahajan, Milind Manaa, Dina Pawitan, Yudi Reichert, Jennifer Ripke, Stephan Sandin, Sven Sklar, Pamela Svantesson, Oscar Reichenberg, Abraham Hultman, Christina M. Devlin, Bernie Roeder, Kathryn Buxbaum, Joseph D.
spellingShingle	Gaugler, Trent Klei, Lambertus Sanders, Stephan J. Bodea, Corneliu A. Goldberg, Arthur P. Lee, Ann B. Mahajan, Milind Manaa, Dina Pawitan, Yudi Reichert, Jennifer Ripke, Stephan Sandin, Sven Sklar, Pamela Svantesson, Oscar Reichenberg, Abraham Hultman, Christina M. Devlin, Bernie Roeder, Kathryn Buxbaum, Joseph D. Most genetic risk for autism resides with common variation
author_facet	Gaugler, Trent Klei, Lambertus Sanders, Stephan J. Bodea, Corneliu A. Goldberg, Arthur P. Lee, Ann B. Mahajan, Milind Manaa, Dina Pawitan, Yudi Reichert, Jennifer Ripke, Stephan Sandin, Sven Sklar, Pamela Svantesson, Oscar Reichenberg, Abraham Hultman, Christina M. Devlin, Bernie Roeder, Kathryn Buxbaum, Joseph D.
author_sort	Gaugler, Trent
title	Most genetic risk for autism resides with common variation
title_short	Most genetic risk for autism resides with common variation
title_full	Most genetic risk for autism resides with common variation
title_fullStr	Most genetic risk for autism resides with common variation
title_full_unstemmed	Most genetic risk for autism resides with common variation
title_sort	most genetic risk for autism resides with common variation
description	A key component of genetic architecture is the allelic spectrum influencing trait variability. For autism spectrum disorder (henceforth autism) the nature of its allelic spectrum is uncertain. Individual risk genes have been identified from rare variation, especially de novo mutations1–8. From this evidence one might conclude that rare variation dominates its allelic spectrum, yet recent studies show that common variation, individually of small effect, has substantial impact en masse9,10. At issue is how much of an impact relative to rare variation. Using a unique epidemiological sample from Sweden, novel methods that distinguish total narrow-sense heritability from that due to common variation, and by synthesizing results from other studies, we reach several conclusions about autism’s genetic architecture: its narrow-sense heritability is ≈54% and most traces to common variation; rare de novo mutations contribute substantially to individuals’ liability; still their contribution to variance in liability, 2.6%, is modest compared to heritable variation.
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137411/
_version_	1613125374058692608

Most genetic risk for autism resides with common variation

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