The Familial Risk of Autism

Sven Sandin, MSc; Paul Lichtenstein, PhD; Ralf Kuja-Halkola, MSc; Henrik Larsson, PhD;
Christina M. Hultman, PhD; Abraham Reichenberg, PhD

IMPORTANCE Autism spectrum disorder (ASD) aggregates in families, but the individual risk
and to what extent this is caused by genetic factors or shared or nonshared environmental
factors remains unresolved.
OBJECTIVE To provide estimates of familial aggregation and heritability of ASD.
DESIGN, SETTING, AND PARTICIPANTS A population-based cohort including 2 049 973
Swedish children born 1982 through 2006.We identified 37 570 twin pairs, 2 642 064 full
sibling pairs, 432 281 maternal and 445 531 paternal half sibling pairs, and 5 799 875 cousin
pairs. Diagnoses of ASD to December 31, 2009 were ascertained.
MAIN OUTCOMES AND MEASURES The relative recurrence risk (RRR) measures familial
aggregation of disease. The RRR is the relative risk of autism in a participant with a sibling or
cousin who has the diagnosis (exposed) compared with the risk in a participant with no
diagnosed family member (unexposed).We calculated RRR for both ASD and autistic disorder
adjusting for age, birth year, sex, parental psychiatric history, and parental age.We estimated
how much of the probability of developing ASD can be related to genetic (additive and
dominant) and environmental (shared and nonshared) factors.
RESULTS In the sample, 14 516 children were diagnosed with ASD, of whom 5689 had autistic
disorder. The RRR and rate per 100 000 person-years for ASD among monozygotic twins was
estimated to be 153.0 (95%CI, 56.7-412.8; rate, 6274 for exposed vs 27 for unexposed ); for
dizygotic twins, 8.2 (95%CI, 3.7-18.1; rate, 805 for exposed vs 55 for unexposed); for full
siblings, 10.3 (95%CI, 9.4-11.3; rate, 829 for exposed vs 49 for unexposed); for maternal half
siblings, 3.3 (95%CI, 2.6-4.2; rate, 492 for exposed vs 94 for unexposed); for paternal half
siblings, 2.9 (95%CI, 2.2-3.7; rate, 371 for exposed vs 85 for unexposed); and for cousins, 2.0
(95%CI, 1.8-2.2; rate, 155 for exposed vs 49 for unexposed). The RRR pattern was similar for
autistic disorder but of slightly higher magnitude.We found support for a disease etiology
including only additive genetic and nonshared environmental effects. The ASD heritability
was estimated to be 0.50 (95%CI, 0.45-0.56) and the autistic disorder heritability was
estimated to 0.54 (95%CI, 0.44-0.64).
CONCLUSIONS AND RELEVANCE Among children born in Sweden, the individual risk of ASD
and autistic disorder increased with increasing genetic relatedness. Heritability of ASD and
autistic disorder were estimated to be approximately 50%. These findings may inform the
counseling of families with affected children.

JAMA. 2014;311(17):1770-1777. doi:10.1001/jama.2014.4144