Most genetic risk for autism resides with common variation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-08

AUTHORS

Trent Gaugler, Lambertus Klei, Stephan J Sanders, Corneliu A Bodea, Arthur P Goldberg, Ann B Lee, Milind Mahajan, Dina Manaa, Yudi Pawitan, Jennifer Reichert, Stephan Ripke, Sven Sandin, Pamela Sklar, Oscar Svantesson, Abraham Reichenberg, Christina M Hultman, Bernie Devlin, Kathryn Roeder, Joseph D Buxbaum

ABSTRACT

A key component of genetic architecture is the allelic spectrum influencing trait variability. For autism spectrum disorder (herein termed autism), the nature of the allelic spectrum is uncertain. Individual risk-associated genes have been identified from rare variation, especially de novo mutations. From this evidence, one might conclude that rare variation dominates the allelic spectrum in autism, yet recent studies show that common variation, individually of small effect, has substantial impact en masse. At issue is how much of an impact relative to rare variation this common variation has. Using a unique epidemiological sample from Sweden, new methods that distinguish total narrow-sense heritability from that due to common variation and synthesis of results from other studies, we reach several conclusions about autism's genetic architecture: its narrow-sense heritability is ∼52.4%, with most due to common variation, and rare de novo mutations contribute substantially to individual liability, yet their contribution to variance in liability, 2.6%, is modest compared to that for heritable variation. More... »

PAGES

881-885

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.3039

DOI

http://dx.doi.org/10.1038/ng.3039

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1049367896

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25038753


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