Results for PAGES (Population-based Autism Genetics and Environment Study), the Swedish study of the heritability of autism. (a) Heritability estimate (95% confidence interval) compared across study designs and analytical methods. Horizontal reference is the PAGES estimate of heritability from SNP genotypes. Twin studies: 1 California twins for strict autism (95% confidence interval: 8–84%), the largest twin study to date using diagnosis only; 2, Swedish twins 9–12 years old (95% confidence interval: 29–91%); 3, Swedish twins 9–12 years old characterized for a quantitative measure of autism (most extreme cutoff; 95% confidence interval: 44–74%). SNP-based estimates of heritability: 4, Swedish family study (95% confidence interval: 44–64%); 5, simplex cases versus population controls (95% confidence interval: 26–73%); 6, multiplex autism cases versus population controls (95% confidence interval: 38–93%). SNP-based estimates from the PAGES study, assuming prevalence K=0.3%; 7, heritability due to common variants using autism cases versus population controls (95% confidence interval: 31–69%); 8, total narrow-sense heritability due to both common and rare variation using smoothed estimates of relatedness (95% confidence interval: 35–71%). (b) Heritability per chromosome versus length in cM. (c) Prevalence by county for all 21 counties in Sweden tallied by birth year cohort. Each boxplot has a lower tail that extends from the minimum county-level prevalence to the 25th percentile; a central box that begins at the 25th percentile and ends at the 75th percentile, with a line demarcating the median prevalence; and an upper tail that extends from the 75th percentile to either (1) the maximum county-level prevalence (in the absence of any outliers) or (2) to a value of the 75th percentile + 1.5 times the vertical distance covered by the box – in this case, any outliers that exceed this end of the tail are noted by circular points on the plot. (d) PAGES heritability versus population prevalence of autism for two estimators of heritability: case-control contrast using SNP genotypes (green); total heritability from smoothed relationships amongst subjects, based on SNP genotypes (blue). Beyond the analysis of the PAGES study we applied meta-analysis of selected h2 estimates (Methods) to obtain h2 = 51.4% (SE = 5.2), which corresponds to a 95% confidence interval of (41.0, 61.8). Contrasting this with the comprehensive estimate of h2 obtained from the Swedish family study (h2 = 54%, SE = 5) produces an estimate of h2 due to rare variants: h2 = 2.6% (SE = 7.2, 95% confidence interval: 0–17%). Hence we conclude that common variants explain the bulk of the heritability for autism, at least 41% of the variability, and rare variants explain at most 17%, based on the upper and lower bounds of the respective 95% confidence intervals.