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Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
This study examined whether executive functions (EFs) might be common features of internalizing and externalizing behavior problems across development. We examined relations between three EF latent variables (a common EF factor and factors specific to updating working memory and shifting sets), constructed from nine laboratory tasks administered at age 17, to latent growth intercept (capturing stability) and slope (capturing change) factors of teacher- and parent-reported internalizing and externalizing behaviors in 885 individual twins aged 7 to 16 years. We then estimated the proportion of intercept–intercept and slope–slope correlations predicted by EF as well as the association between EFs and a common psychopathology factor (P factor) estimated from all 9 years of internalizing and externalizing measures. Common EF was negatively associated with the intercepts of teacher-rated internalizing and externalizing behavior in males, and explained 32% of their covariance; in the P factor model, common EF was associated with the P factor in males. Shifting-specific was positively associated with the externalizing slope across sex. EFs did not explain covariation between parent-rated behaviors. These results suggest that EFs are associated with stable problem behavior variation, explain small proportions of covariance, and are a risk factor that that may depend on gender.
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