A novel sibling-based design to quantify genetic and shared environmental effects: application to drug abuse, alcohol use disorder and criminal behavior

Abstract

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

The Genetic Epidemiology of Treated Major Depression in Sweden

“…These results provide no support for the hypothesis that twin studies overestimate the heritability of major depression. Our results are consistent with previous analyses using sibling designs that found that standard twin models do not overestimate the heritability of alcohol use disorder, drug abuse, or criminality (19). Inflated estimates from twin studies for the heritability of major depression are unlikely contributors to the "missing heritability problem.…”

“…While SNP heritability might underestimate true heritability for many reasons, an additional explanation is that twin studies overestimate heritability (15)(16)(17)(18). With Scandinavian registries, it has become possible to compare heritability estimates from twin studies with those obtained from other genetically informative relationships that are not susceptible to the methodological problems of twin studies, although they have potential limitations of their own (19,20).…”

Gene–environment interaction of monoamine oxidase A in relation to antisocial behaviour: current and future directions

“…However, a shared environment is significant only for the adolescent-limited ASB and explains only 30–40% of the variance (Eley et al 2003 ). Twin studies have been criticized for upwardly biased estimates that might contribute to the difference in estimated heritability between these two forms of ASB; therefore, a total population sibling-based or mixed design that uses both population-based sibling and twin designs has been proposed (Kendler et al 2015 , 2016 ). However, the explanatory effect derived from studies involving twins, adopted siblings and population siblings have important limitations in terms of G×E research because models of such designs often pre-suppose non-interaction effects and often lack the G×E term in their models (Plomin et al 1977 ).…”

ADHD, Lifestyles and Comorbidities: A Call for an Holistic Perspective – from Medical to Societal Intervening Factors

“…Substance abuse and alcoholism are widely known to be running in families, and research shows both environmental and genetic causes (Thapar, 2015; Kendler et al, 2016). A meta-analysis in Sweden reviewing substance abuse and addiction among ADHD populations and their relatives, found a strong correlation among the two.…”