1. Most genetic risk for autism resides with common variation
- Author
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Jennifer Reichert, Dina Manaa, Ann B. Lee, Stephan Ripke, Kathryn Roeder, Stephen Sanders, Pamela Sklar, Yudi Pawitan, Arthur P. Goldberg, Lambertus Klei, Corneliu A. Bodea, Christina M. Hultman, Bernie Devlin, Trent Gaugler, Joseph D. Buxbaum, Abraham Reichenberg, Sven Sandin, Milind Mahajan, and Oscar Svantesson
- Subjects
Genetics ,Extramural ,Biology ,Heritability ,medicine.disease ,Genetic architecture ,Article ,Variation (linguistics) ,mental disorders ,medicine ,Autism ,Heritability of autism ,Genetic risk ,Allele - Abstract
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.
- Published
- 2014