It is not immediately clear what might be the driving force behind differences in genetic influences on AUD symptoms/problems between ascertained and epidemiological samples. Heritability estimates calculated either by GCTA (Yang et al., 2011) or GenABEL differed between samples, but not systematically across sample types (ALSPAC: 0.06, FinnTwin12: 0.32, COGA: 0.35, COGA young adults: 0.25, IASPSAD: 0.04). Post-hoc sample comparisons did not indicate obvious systematic differences between the sample types based on characteristics such as internalizing/externalizing disorder symptoms (e.g. major depression, anti-social personality disorder) or related traits and behaviors (e.g. personality, other substance use), although differences in the measures collected between studies preclude a direct statistical comparison of many such characteristics (details available upon request). However, the polygenic risk scores based on GWAS weights for alcohol problems did not show a differential pattern of predicting these traits across population-based and ascertained samples either, indicating that the differential prediction of alcohol problems outcomes between sample types seen in our results was not simply driven by sample differences in internalizing/externalizing traits or comorbidities, as suggested by some AUD typologies (e.g. Cloninger et al., 1988).
