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    The Associations Between Polygenic Risk, Sensation Seeking, Social Support, and Alcohol Use in Adulthood
    (Amer Psychological Assoc, 2021) Su, Jinni; Kuo, Sally I-Chun; Aliev, Fazil; Chan, Grace; Edenberg, Howard J.; Kamarajan, Chella; McCutcheon, Vivia V.
    Genetic predispositions play an important role in alcohol use. Understanding the psychosocial mechanisms through which genetic risk unfolds to influence alcohol use outcomes is critical for identifying modifiable targets and developing prevention and intervention efforts. In this study, we examined the role of sensation seeking and social support from family and friends in linking genetic risk to alcohol use. We also examined the role of social support in moderating the associations between genetic risk and sensation seeking and alcohol use. Data were drawn from a sample of 2,836 European American adults from the Collaborative Study on the Genetics of Alcoholism (46% male, mean age = 35.65, standard deviation [SD] = 10.78). Results from path analysis indicated that genome-wide polygenic scores for alcohol consumption (alc-GPS) were associated with higher sensation seeking, which in turn was associated with higher levels of alcohol use. alc-GPS was also associated with higher alcohol use indirectly via lower levels of family support. In addition, high friend support attenuated the association between alc-GPS and sensation seeking and alcohol use. The pattern of associations was similar for males and females, with some differences in the associations between social support and alcohol use observed across age. Our findings highlight the important role of intermediate phenotypes and gene-environment interplay in the pathways of risk from genetic predispositions to complex alcohol use outcomes.
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    GENE-BY-INTERVENTION EFFECTS ON ALCOHOL DEPENDENCE SYMPTOMS IN EMERGING ADULTHOOD
    (Elsevier, 2019) Neale, Zoe; Kuo, Sally I-Chun; Aliev, Fazil; Barr, Peter; Su, Jinni; Elam, Kit; Ha, Thao
    [No abstract available]
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    Influence of Parental Alcohol Dependence Symptoms and Parenting on Adolescent Risky Drinking and Conduct Problems: A Family Systems Perspective
    (Wiley, 2018) Su, Jinni; Kuo, Sally I-Chun; Aliev, Fazil; Guy, Mignonne C.; Derlan, Chelsea L.; Edenberg, Howard J.; Nurnberger, John I., Jr.
    BackgroundParental alcohol problems are associated with adverse adolescent outcomes such as risky drinking and conduct problems. Important questions remain about the unique roles of fathers' and mothers' alcohol problems and differences and/or similarities in pathways of risk across ethnicity and gender. In this study, we used a family systems approach to consider spillover and crossover effects of fathers' and mothers' alcohol problems (number of alcohol dependence symptoms [ADS]) and parenting behaviors in relation to adolescents' risky drinking and conduct problems. MethodsThe sample included 1,282 adolescents (aged 12 to 17) and their parents from the Collaborative Study on the Genetics of Alcoholism. Parents completed the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA), and adolescents completed an adolescent version of SSAGA. Data were analyzed using multivariate structural equationmodeling. ResultsFathers' ADS count was associated with higher adolescent risky drinking and conduct problems indirectly via disruption to fathers' and mothers' positive parenting behaviors, whereas mothers' ADS count was not associated with adolescents' risky drinking and conduct problems directly or indirectly via positive parenting behaviors. No differences in these associations were found across ethnic background and offspring gender. ConclusionsFindings highlight the importance of considering the unique roles of fathers' and mothers' ADS in influencing family processes and adolescent outcomes.
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    RISK PREDICTION WITH POLYGENIC RISK SCORES IN MULTI-ETHNIC SAMPLES
    (Elsevier, 2019) Aliev, Fazil; Salvatore, Jessica; Su, Jinni; Kuo, Sally I-Chun; Barr, Peter; Agrawal, Arpana; Cho, Seung Bin
    [No abstract available]
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    Sibling comparisons elucidate the associations between educational attainment polygenic scores and alcohol, nicotine and cannabis
    (Wiley, 2020) Salvatore, Jessica E.; Barr, Peter B.; Stephenson, Mallory; Aliev, Fazil; Kuo, Sally I-Chun; Su, Jinni; Agrawal, Arpana
    Background and Aims The associations between low educational attainment and substance use disorders (SUDs) may be related to a common genetic vulnerability. We aimed to elucidate the associations between polygenic scores for educational attainment and clinical criterion counts for three SUDs (alcohol, nicotine and cannabis). Design Polygenic association and sibling comparison methods. The latter strengthens inferences in observational research by controlling for confounding factors that differ between families. Setting Six sites in the United States. Participants European ancestry participants aged 25 years and older from the Collaborative Study on the Genetics of Alcoholism (COGA). Polygenic association analyses included 5582 (54% female) participants. Sibling comparisons included 3098 (52% female) participants from 1226 sibling groups nested within the overall sample. Measurements Outcomes included criterion counts for DSM-5 alcohol use disorder (AUDSX), Fagerstrom nicotine dependence (NDSX) and DSM-5 cannabis use disorder (CUDSX). We derived polygenic scores for educational attainment (EduYears-GPS) using summary statistics from a large (> 1 million) genome-wide association study of educational attainment. Findings In polygenic association analyses, higher EduYears-GPS predicted lower AUDSX, NDSX and CUDSX [P < 0.01, effect sizes (R-2) ranging from 0.30 to 1.84%]. These effects were robust in sibling comparisons, where sibling differences in EduYears-GPS predicted all three SUDs (P < 0.05, R-2 0.13-0.20%). Conclusions Individuals who carry more alleles associated with educational attainment tend to meet fewer clinical criteria for alcohol, nicotine and cannabis use disorders, and these effects are robust to rigorous controls for potentially confounding factors that differ between families (e.g. socio-economic status, urban-rural residency and parental education).
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    Using polygenic scores for identifying individuals at increased risk of substance use disorders in clinical and population samples
    (Nature Publishing Group, 2020) Barr, Peter B.; Ksinan, Albert; Su, Jinni; Johnson, Emma C.; Meyers, Jacquelyn L.; Wetherill, Leah; Latvala, Antti
    Genome-wide, polygenic risk scores (PRS) have emerged as a useful way to characterize genetic liability. There is growing evidence that PRS may prove useful for early identification of those at increased risk for certain diseases. The current potential of PRS for alcohol use disorders (AUD) remains an open question. Using data from both a population-based sample [the FinnTwin12 (FT12) study] and a high-risk sample [the Collaborative Study on the Genetics of Alcoholism (COGA)], we examined the association between PRSs derived from genome-wide association studies (GWASs) of (1) alcohol dependence/alcohol problems, (2) alcohol consumption, and (3) risky behaviors with AUD and other substance use disorder (SUD) criteria. These PRSs explain similar to 2.5-3.5% of the variance in AUD (across FT12 and COGA) when all PRSs are included in the same model. Calculations of area under the curve (AUC) show PRS provide only a slight improvement over a model with age, sex, and ancestral principal components as covariates. While individuals in the top 20, 10, and 5% of the PRS distribution had greater odds of having an AUD compared to the lower end of the continuum in both COGA and FT12, the point estimates at each threshold were statistically indistinguishable. Those in the top 5% reported greater levels of licit (alcohol and nicotine) and illicit (cannabis and opioid) SUD criteria. PRSs are associated with risk for SUD in independent samples. However, usefulness for identifying those at increased risk in their current form is modest, at best. Improvement in predictive ability will likely be dependent on increasing the size of well-phenotyped discovery samples.