scholarly journals Drinking and smoking polygenic risk is associated with childhood and early-adulthood psychiatric and behavioral traits independently of substance use and psychiatric genetic risk

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Flavio De Angelis ◽  
Frank R. Wendt ◽  
Gita A. Pathak ◽  
Daniel S. Tylee ◽  
Aranyak Goswami ◽  
...  
Keyword(s):  
Substance Use ◽  
Young Adults ◽  
Tobacco Smoking ◽  
Alcohol Drinking ◽  
Smoking Initiation ◽  
European Ancestry ◽  
Polygenic Risk ◽  
Behavioral Traits ◽  
Wide Range ◽  
Children And Young Adults

AbstractAlcohol drinking and tobacco smoking are hazardous behaviors associated with a wide range of adverse health outcomes. In this study, we explored the association of polygenic risk scores (PRS) related to drinks per week, age of smoking initiation, smoking initiation, cigarettes per day, and smoking cessation with 433 psychiatric and behavioral traits in 4498 children and young adults (aged 8–21) of European ancestry from the Philadelphia neurodevelopmental cohort. After applying a false discovery rate multiple testing correction accounting for the number of PRS and traits tested, we identified 36 associations related to psychotic symptoms, emotion and age recognition social competencies, verbal reasoning, anxiety-related traits, parents’ education, and substance use. These associations were independent of the genetic correlations among the alcohol-drinking and tobacco-smoking traits and those with cognitive performance, educational attainment, risk-taking behaviors, and psychopathology. The removal of participants endorsing substance use did not affect the associations of each PRS with psychiatric and behavioral traits identified as significant in the discovery analyses. Gene-ontology enrichment analyses identified several neurobiological processes underlying mechanisms of the PRS associations we report. In conclusion, we provide novel insights into the genetic overlap of smoking and drinking behaviors in children and young adults, highlighting their independence from psychopathology and substance use.

scholarly journals Drinking and smoking polygenic risk is associated with neurodevelopmental outcomes of children and young adults independently of psychopathology and substance use.

2020 ◽  
Author(s):  
Flavio De Angelis ◽  
Frank Wendt ◽  
Gita A Pathak ◽  
Daniel Tylee ◽  
aranyak goswami ◽  
...  
Keyword(s):  
Substance Use ◽  
Young Adults ◽  
Tobacco Smoking ◽  
Alcohol Drinking ◽  
Smoking Initiation ◽  
European Ancestry ◽  
Multiple Testing Correction ◽  
Polygenic Risk ◽  
Wide Range ◽  
Children And Young Adults

Background: Alcohol drinking and tobacco smoking are hazardous behaviors associated with a wide range of adverse health outcomes, including many mental and physical disorders. Methods: To investigate the pleiotropic mechanisms linking these traits to cognitive and behavioral development, we explored the association of polygenic risk scores (PRS) related to drinks per week (DPW), age of smoking initiation (ASI), smoking initiation (SI), cigarettes per day (CPD), and smoking cessation (SC) with 433 neurodevelopmental features in 4,498 children and young adults of European ancestry from the Philadelphia neurodevelopmental cohort (PNC). This sample was not enriched for specific psychiatric traits, but 21% of the PNC participants endorsed substance use. Results: After applying a false discovery rate multiple testing correction accounting for the number of PRS and traits tested, we identified 36 associations related to psychotic symptoms, emotion and age recognition social competencies, verbal reasoning, anxiety-related traits, parents education, and substance use. These associations were independent of the genetic correlations among the alcohol-drinking and tobacco-smoking traits and those with cognitive performance, educational attainment, risk-taking behaviors, and psychopathology. The removal of participants endorsing substance use did not affect the associations of each PRS with neurodevelopmental traits identified as significant in the discovery analyses. Gene-ontology enrichment analyses identified several neurobiological processes underlying mechanisms of the PRS associations we report. These were mainly related to brain connectivity. Conclusions: We provide novel insights into the genetic overlap of smoking and drinking behaviors with neurodevelopment in children and young adults, highlighting their independence from psychopathology and other substance use.

scholarly journals Assessment of Polygenic Architecture and Risk Prediction based on Common Variants Across Fourteen Cancers

2019 ◽  
Author(s):  
Yan Zhang ◽  
Amber N. Wilcox ◽  
Haoyu Zhang ◽  
Parichoy Pal Choudhury ◽  
Douglas F. Easton ◽  
...  
Keyword(s):  
Association Studies ◽  
Disease Incidence ◽  
Effect Sizes ◽  
European Ancestry ◽  
Risk Scores ◽  
Average Risk ◽  
Genome Wide Association Studies ◽  
Lymphoid Leukemia ◽  
Polygenic Risk ◽  
Wide Range

AbstractWe analyzed summary-level data from genome-wide association studies (GWAS) of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) contributing to risk, as well as the distribution of their associated effect sizes. All cancers evaluated showed polygenicity, involving at a minimum thousands of independent susceptibility variants. For some malignancies, particularly chronic lymphoid leukemia (CLL) and testicular cancer, there are a larger proportion of variants with larger effect sizes than those for other cancers. In contrast, most variants for lung and breast cancers have very small associated effect sizes. For different cancer sites, we estimate a wide range of GWAS sample sizes, required to explain 80% of GWAS heritability, varying from 60,000 cases for CLL to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores, compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that polygenic risk scores have substantial potential for risk stratification for relatively common cancers such as breast, prostate and colon, but limited potential for other cancer sites because of modest heritability and lower disease incidence.

Evaluation of modifiable factors and polygenic risk score in thyroid cancer

2021 ◽  
Author(s):  
Tung Hoang ◽  
Quy Nguyen Ngoc ◽  
Jeonghee Lee ◽  
Eun Kyung Lee ◽  
Yul Hwangbo ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Alcohol Consumption ◽  
Risk Score ◽  
Tobacco Smoking ◽  
Cumulative Effect ◽  
European Ancestry ◽  
Polygenic Risk Score ◽  
Regular Exercise ◽  
Polygenic Risk ◽  
Modifiable Factors

The cumulative effect of single-nucleotide polymorphisms (SNPs) on thyroid cancer has been adequately defined in individuals of European ancestry; however, similar evidence in the Korean population is limited. This study aimed to investigate the influence of modifiable factors and the polygenic risk score (PRS) and their interactive and combined effects on thyroid cancer. Using data from the Cancer Screenee Cohort, this study included 759 thyroid cancer cases and 759 age- and sex-matched controls. We examined the effects of tobacco smoking, alcohol consumption, and regular exercise habits, body mass index (BMI), and the PRS of 6 SNPs on thyroid cancer. Odds ratios (ORs) and 95% confidence intervals (CIs) for the associations were obtained using a conditional logistic regression model. The results indicated that family history, obesity, and the unweighted and weighted PRS were independently associated with susceptibility to thyroid cancer, with ORs (95% CIs) of 2.96 (1.63-5.36), 1.72 (1.20-2.48), 1.46 (1.10-1.93), and 1.56 (1.19-2.03), respectively, whereas the effect of smoking, drinking, and regular exercise was not significant. The contribution of the PRS remained after stratifying participants with healthy behaviours, such as nonsmokers/nondrinkers, and regular exercise. Although the PRS did not significantly contribute to the risk for thyroid cancer when participants were stratified according to BMI, BMI and the PRS had a cumulative effect on thyroid cancer risk. The combined effect of genetic polymorphisms on predisposition to thyroid cancer may differ based on tobacco smoking, alcohol consumption, regular exercise behaviours and cumulative BMI. Larger population-based studies are needed to validate these findings.

scholarly journals Genetic liability for substance use associated with medical comorbidities in electronic health records of African- and European-ancestry individuals

2021 ◽  
Author(s):  
Emily E. Hartwell ◽  
Alison K. Merikangas ◽  
Shefali S. Verma ◽  
Marylyn D. Ritchie ◽  
Henry R. Kranzler ◽  
...  
Keyword(s):  
Substance Use ◽  
Genetic Risk ◽  
Smoking Initiation ◽  
European Ancestry ◽  
Risk Scores ◽  
Opioid Use ◽  
Genetic Liability ◽  
Association Analyses ◽  
Electronic Health ◽  
Trait Associations

AbstractPolygenic risk scores (PRS) represent an individual’s summed genetic risk for a trait and can serve as biomarkers for disease. Less is known about the utility of PRS as a means to quantify genetic risk for substance use disorders (SUDs) than for many other traits. Nonetheless, the growth of large, electronic health record-based biobanks makes it possible to evaluate the association of SUD PRS with other traits. We calculated PRS for smoking initiation, alcohol use disorder (AUD), and opioid use disorder (OUD) using summary statistics from the Million Veteran Program sample. We then tested the association of each PRS with its primary phenotype in the Penn Medicine BioBank (PMBB) using all available genotyped participants of African or European ancestry (AFR and EUR, respectively) (N=18,612). Finally, we conducted phenome-wide association analyses (PheWAS) separately by ancestry and sex to test for associations across disease categories. Tobacco use disorder was the most common SUD in the PMBB, followed by AUD and OUD, consistent with the population prevalence of these disorders. All PRS were associated with their primary phenotype in both ancestry groups. PheWAS results yielded cross-trait associations across multiple domains, including psychiatric disorders and medical conditions. SUD PRS were associated with their primary phenotypes, however they are not yet predictive enough to be useful diagnostically. The cross-trait associations of the SUD PRS are indicative of a broader genetic liability. Future work should extend findings to additional population groups and for other substances of abuse.

scholarly journals Association of genetic liability to smoking initiation with e-cigarette use in young adults

2020 ◽  
Author(s):  
Jasmine N Khouja ◽  
Robyn E Wootton ◽  
Amy E Taylor ◽  
George Davey Smith ◽  
Marcus R Munafò
Keyword(s):  
Young Adults ◽  
Socioeconomic Position ◽  
Risk Taking ◽  
Smoking Initiation ◽  
Negative Control ◽  
European Ancestry ◽  
Cigarette Use ◽  
Genetic Liability ◽  
Externalising Disorders ◽  
Shared Genetic

AbstractBackgroundSmoking and e-cigarette use are strongly associated, but it is currently unclear whether this association is causal, or due to shared factors that influence both behaviours such as a shared genetic liability. The aim of this study was to investigate whether polygenic risk scores (PRS) for smoking initiation are associated with ever use of e-cigarettes.Methods and FindingsPRS of smoking initiation were calculated for young adults (aged 23 to 26 years) of European ancestry in the Avon Longitudinal Study of Parents and Children using the GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) summary statistics. Five thresholds ranging from 5×10−8 to 0.5 were used to calculate five PRS for each individual. Using logistic regression, we investigated the association between smoking initiation PRS and both self-reported smoking initiation and self-reported e-cigarette use, as well as a number of negative control outcomes (socioeconomic position at birth, externalising disorders in childhood and risk-taking in young adulthood). We observed positive associations of similar magnitude between smoking initiation PRS and both smoking initiation (OR = 1.29, 95% CI 1.19 to 1.39) and ever e-cigarette use (OR = 1.24, 95% CI 1.14 to 1.34) by the age of 24 years. At lower p-value thresholds, we observed an association between smoking initiation PRS and ever e-cigarette use among never smokers. We also found evidence of associations between smoking initiation PRS and some negative control outcomes, particularly when less stringent p-value thresholds were used but also at the strictest threshold (e.g., gambling, number of sexual partners, conduct disorder at 7 years, and parental socioeconomic position at birth).ConclusionsOur results indicate that there may be a shared genetic aetiology between smoking and e-cigarette use, and also with socioeconomic position, externalising disorders in childhood, and risky behaviour more generally. Taken together, this indicates that there may be a common genetic vulnerability to both smoking and e-cigarette use, which may reflect a broad risk-taking phenotype.

scholarly journals Gene-Gene interactions and pleiotropy in the brain nicotinic pathway associated with the heaviness and precocity of tobacco smoking among outpatients with multiple substance use disorders

2019 ◽  
Author(s):  
Romain Icick ◽  
Morgane Besson ◽  
El-Hadi Zerdazi ◽  
Nathalie Prince ◽  
Vanessa Bloch ◽  
...  
Keyword(s):  
Substance Use ◽  
Substance Use Disorders ◽  
Nicotinic Acetylcholine Receptors ◽  
Tobacco Smoking ◽  
Acetylcholine Receptors ◽  
Age At Onset ◽  
Smoking Initiation ◽  
Daily Smoking ◽  
Gene Interactions ◽  
Nucleotide Polymorphisms

AbstractIntroductionTobacco smoking is a major health burden worldwide, especially in populations suffering from other substance use disorders (SUDs). Several smoking phenotypes have been associated with single nucleotide polymorphisms (SNPs) of nicotinic acetylcholine receptors (nAChRs). Yet, little is known about the genetics of tobacco smoking in populations with other SUDs, particularly regarding gene-gene interactions and pleiotropy, which are likely involved in the polygenic architecture of SUDs. Thus, we undertook a candidate pathway association study of nAChR-related genes and smoking phenotypes in a sample of SUD patients.Methods493 patients with genetically-verified Caucasian ancestry were characterized extensively regarding patterns of tobacco smoking, other SUDs, and 83 SNPs from the nicotinic pathway, encompassing all brain nAChR subunits and metabolic/chaperone/trafficking proteins. Single-SNP, gene-based and SNP × SNP interactions analyses were performed to investigate associations with relevant tobacco smoking phenotypes. This included Bayesian analyses to detect pleiotropy, and adjustment on clinical and sociodemographic confounders.ResultsAfter multiple adjustment, we found independent associations between CHRNA3 rs8040868 and a higher number of cigarettes per day (CPD), and between RIC3 rs11826236 and a lower age at smoking initiation. Two SNP × SNP interactions were associated with age at onset (AAO) of daily smoking. There was pleiotropy regarding three SNPs in CHRNA3 (CPD, AAO daily smoking), ACHE (CPD, HSI) and CHRNB4 (CPD, both AAOs).DiscussionDespite limitations, the present study shows that the genetics of tobacco smoking in SUD patients are both distinct and partially shared across smoking phenotypes, and involve metabolic and chaperone effectors of the nicotinic pathway.

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