Polygenic risk scores for schizophrenia and bipolar disorder associate with addiction

Abstract

We use polygenic risk scores (PRSs) for schizophrenia (SCZ) and bipolar disorder (BPD) to predict smoking, and addiction to nicotine, alcohol or drugs in individuals not diagnosed with psychotic disorders. Using PRSs for 144 609 subjects, including 10 036 individuals admitted for in‐patient addiction treatment and 35 754 smokers, we find that diagnoses of various substance use disorders and smoking associate strongly with PRSs for SCZ (P = 5.3 × 10−50–1.4 × 10−6) and BPD (P = 1.7 × 10−9–1.9 × 10−3), showing shared genetic etiology between psychosis and addiction. Using standardized scores for SCZ and BPD scaled to a unit increase doubling the risk of the corresponding disorder, the odds ratios for alcohol and substance use disorders range from 1.19 to 1.31 for the SCZ‐PRS, and from 1.07 to 1.29 for the BPD‐PRS. Furthermore, we show that as regular smoking becomes more stigmatized and less prevalent, these biological risk factors gain importance as determinants of the behavior.

Recent Advances in the Genetics of Schizophrenia

“…Hamshere et al [95] showed an overlap of schizophrenia PRS with attention-deficit hyperactivity disorder (ADHD), while the Cross-Disorder Group of the PGC published on overlaps across five disorders, autism, ADHD, BP, MDD, and schizophrenia showing strongest overlaps between schizophrenia BP and MDD [96]. Others have shown positive correlations of schizophrenia PRS with the risk for posttraumatic stress disorder [97], addiction [98], and cortical thinning in patients [99]. In contrast, a large study from Iceland found that an increased score correlated with higher creativity, using membership in artistic societies and creative profession as a proxy [100].…”

Relationships between substance abuse/dependence and psychiatric disorders based on polygenic scores

“…Taking into account the influence of ascertainment 19 and social context, 20 there is a need to generalize these results to other populations, which may differ in social environment, and using other ascertainment strategies. In this work, we analyzed the effect of PGSs for different psychiatric disorders in relation to substance abuse/dependence in subjects from Galicia.…”

“…This distribution was used to estimate the P value of the real dataset using a significance level of 0.05.These analyses were performed twice, using the whole sample or those cases with alcohol abuse/dependence, to replicate the results of Reginsson et al20 By this way, covariates such as age and MDS dimensions are maintained.…”

Genome-wide association meta-analysis of cocaine dependence: Shared genetics with comorbid conditions

“…To our knowledge, this is the first report of a shared genetic etiology between cocaine dependence and ADHD, antisocial behavior, risk-taking behavior and children's aggressive behavior based on genome-wide data. Previous studies have reported significant PRS associations between cocaine dependence and SCZ or MDD (Carey et al 2016;Hartz et al 2017;Reginsson et al 2018), and also between SUD and other psychiatric disorders (Du Rietz et al 2017;Gurriarán et al 2018), although our study used the largest sample of cocaine dependence for this type of analysis so far. This correlation can reflect biological pleiotropy, where similar genetic mechanisms influence more than one trait, or mediated pleiotropy, where one phenotype is causally related to a second phenotype, so that the variants associated with this phenotype are indirectly associated with the second one.…”

“…Such comorbidity is associated with an increase of severity for all disorders, although it is unclear whether this relationship is causal or the result of shared genetic and/or environmental risk factors. Some studies have started to inspect these relationships using both genetic correlation and polygenic risk score approaches, supporting the hypothesized role of shared genetic risk factors in the lifetime co-occurrence of several psychiatric disorders and SUD (Carey et al 2016;Hartz et al 2017;Du Rietz et al 2017;Reginsson et al 2018). …”