Publication
Familial risk and heritability of intellectual disability: a population-based cohort study in Sweden.
Publisher:
Wiley
Date:
18-12-2022
DOI:
10.1111/JCPP.13560
Abstract: Intellectual disability (ID) aggregates in families, but factors affecting in idual risk and heritability estimates remain unknown. A population-based family cohort study of 4,165,785 in iduals born 1973-2013 in Sweden, including 37,787 ID in iduals and their relatives. The relative risks (RR) of ID with 95% confidence intervals (95% CI) were obtained from stratified Cox proportional-hazards models. Relatives of ID in iduals were compared to relatives of unaffected in iduals. Structural equation modeling was used to estimate heritability. Relatives of ID in iduals were at increased risk of ID compared to in iduals with unaffected relatives. The RR of ID among relatives increased proportionally to the degree of genetic relatedness with ID probands 256.70(95% CI 161.30-408.53) for monozygotic twins, 16.47(13.32-20.38) for parents, 14.88(12.19-18.16) for children, 7.04(4.67-10.61) for dizygotic twins, 8.38(7.97-8.83) for full siblings, 4.56(4.02-5.16) for maternal, 2.90(2.49-3.37) for paternal half-siblings, 3.03(2.61-3.50) for nephews/nieces, 2.84(2.45-3.29) for uncles/aunts, and 2.04(1.91-2.20) for cousins. Lower RRs were observed for siblings of probands with chromosomal abnormalities (RR 5.53, 4.74-6.46) and more severe ID (mild RR 9.15, 8.55-9.78, moderate RR 8.13, 7.28-9.08, severe RR 6.80, 5.74-8.07, and profound RR 5.88, 4.52-7.65). Male sex of relative and maternal line of relationship with proband was related to higher risk (RR 1.33, 1.25-1.41 for brothers vs. sisters and RR 1.49, 1.34-1.68 for maternal vs. paternal half-siblings). ID was substantially heritable with 0.95(95% CI 0.93-0.98) of the variance in liability attributed to genetic influences. The risk estimates will benefit researchers, clinicians, families in understanding the risk of ID in the family and the whole population. The higher risk of ID related to male sex and maternal linage will be of value for planning and interpreting etiological studies in ID.
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