Heritability of Autism Spectrum Disorder in a UK Population-Based Twin Sample

Abstract

Twin studies of autism,^1-6 conducted from 1977 onward, provided the first clear evidence that genetic factors were etiologically important. Recent reviews of this literature^5,7-9 show general agreement across studies that concordance for autism in monozygotic (MZ) twin pairs is typically at least double that in dizygotic (DZ) twin pairs, resulting in high heritability estimates (60%-90%)^10-14 and suggesting little influence of shared environmental factors. Two twin studies^15,16 stand in contrast and reported only moderate heritability (21%-38%), with a substantial shared environmental component explaining 58% to 78% of the variance in liability to autism spectrum disorder (ASD). In comparison, 1 recent twin study did not confirm significant shared environmental effects and reported heritability of 95%.¹⁷ In addition, a large population study of extended families (approximately 2 million individuals)¹⁸ reported estimates of 50% for heritability and nonshared environmental factors. Most recently, in the same population, molecular genetic analysis¹⁹ indicated that 95% of variance in ASD is accounted for by common allelic variants, supporting a polygenic model. This finding contrasts markedly with heritability estimates of around 0 derived from single-nucleotide polymorphism data (GCTA) in an arguably underpowered sample.²⁰ Given the interest in possible environmental factors in the etiology of autism, these contradictory findings have reopened the discussion of high heritability and the possibility that findings may be biased by sample selection and screening. The first aim of the present study was to examine the relative importance of genetic and environmental factors in liability to ASD in a large systematically screened, population-based twin sample.