Most genetic risk for autism resides with common variation

By Trent L. Gaugler, L. Klei, Stephan J Sanders, C. Bodea, A. Goldberg, Ann B. Lee, M. Mahajan, Dina Manaa, Y. Pawitan, J. Reichert and 9 more. Nature Genetics, 2014

1,198 citations recorded by the source corpus.

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.

Subfields: Cognitive Neuroscience, Epidemiology, Genetics

View Paper: https://www.semanticscholar.org/paper/ed99d8ed8d1f83ac18443f3b73fbc0b9038250be

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cognitive Neuroscience

1. Stephen V. Faraone
2. Michael Rutter
3. F. Happé

In Epidemiology

1. Stephen V. Faraone
2. M. Ungar

In Genetics

1. Christine Ladd-Acosta
2. Patrick F. Sullivan
3. Jordan W. Smoller
4. Michael Rutter
5. F. Happé

Citations in the corpus

• The Changing Epidemiology of Autism Spectrum Disorders (2016, background): “, polygenic risk, is now being recognized as an important indicator of risk for ASD as well as for other psychiatric disorders (47, 65).”
• Psychiatric Genomics: An Update and an Agenda (2017, background): “All common psychiatric disorders with suf fi - ciently large samples have a predominant common disease/ common variant contribution (26 – 28).”
• Heritability of autism spectrum disorders: a meta‐analysis of twin studies (2015, background): “There is evidence for the contribution of both common variants and rare mutations (Gaugler et al., 2014; Iossifov et al., 2015) and at this point it is simply not possible to definitively decide on one model over the other.”