A novel sibling-based design to quantify genetic and shared environmental effects: application to drug abuse, alcohol...

Twin studies have been criticized for upwardly biased estimates that might contribute to the missing heritability problem.

We identified, from the general Swedish population born 1960-1990, informative sibships containing a proband, one reared-together full- or half-sibling and a full-, step- or half-sibling with varying degrees of childhood cohabitation with the proband. Estimates of genetic, shared and individual specific environment for drug abuse (DA), alcohol use disorder (AUD) and criminal behavior (CB), assessed from medical, legal or pharmacy registries, were obtained using Mplus.

Aggregate estimates of additive genetic effects for DA, AUD and CB obtained separately in males and females varied from 0.46 to 0.73 and agreed with those obtained from monozygotic and dizygotic twins from the same population. Of 54 heritability estimates from individual classes of informative sibling trios (3 syndromes × 9 classes of trios × 2 sexes), heritability estimates from the siblings were lower, tied and higher than those from obtained from twins in 26, one and 27 comparisons, respectively. By contrast, of 54 shared environmental estimates, 33 were lower than those found in twins, one tied and 20 were higher.

With adequate information, human populations can provide many methods for estimating genetic and shared environmental effects. For the three externalizing syndromes examined, concerns that heritability estimates from twin studies are upwardly biased or were not generalizable to more typical kinds of siblings were not supported. Overestimation of heritability from twin studies is not a likely explanation for the missing heritability problem.