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    Can Genetics Predict Response to Complex Behavioral Interventions? Evidence from a Genetic Analysis of the Fast Track Randomized Control Trial
    (Wiley, 2015) Albert, Dustin; Belsky, Daniel W.; Crowley, D. Max; Latendresse, Shawn J.; Aliev, Fazil; Riley, Brien; Sun, Cuie
    Early interventions are a preferred method for addressing behavioral problems in high-risk children, but often have only modest effects. Identifying sources of variation in intervention effects can suggest means to improve efficiency. One potential source of such variation is the genome. We conducted a genetic analysis of the Fast Track randomized control trial, a 10-year-long intervention to prevent high-risk kindergarteners from developing adult externalizing problems including substance abuse and antisocial behavior. We tested whether variants of the glucocorticoid receptor gene NR3C1 were associated with differences in response to the Fast Track intervention. We found that in European-American children, a variant of NR3C1 identified by the single-nucleotide polymorphism rs10482672 was associated with increased risk for externalizing psychopathology in control group children and decreased risk for externalizing psychopathology in intervention group children. Variation in NR3C1 measured in this study was not associated with differential intervention response in African-American children. We discuss implications for efforts to prevent externalizing problems in high-risk children and for public policy in the genomic era.
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    Molecular Genetic Influences on Normative and Problematic Alcohol Use in a Population-Based Sample of College Students
    (Frontiers Media Sa, 2017) Webb, Bradley T.; Edwards, Alexis C.; Wolen, Aaron R.; Salvatore, Jessica E.; Aliev, Fazil; Riley, Brien P.; Sun, Cuie
    Background : Genetic factors impact alcohol use behaviors and these factors may become increasingly evident during emerging adulthood. Examination of the effects of individual variants as well as aggregate genetic variation can clarify mechanisms underlying risk. Methods : We conducted genome-wide association studies (GWAS) in an ethnically diverse sample of college students for three quantitative outcomes including typical monthly alcohol consumption, alcohol problems, and maximum number of drinks in 24 h. Heritability based on common genetic variants (h(SNP)(2)) was assessed. We also evaluated whether risk variants in aggregate were associated with alcohol use outcomes in an independent sample of young adults. Results : Two genome-wide significant markers were observed: rs11201929 in GRID1 for maximum drinks in 24 h, with supportive evidence across all ancestry groups; and rs73317305 in SAMD12 (alcohol problems), tested only in the African ancestry group. The h(SNP)(2) estimate was 0.19 (SE = 0.11) for consumption, and was non-significant for other outcomes. Genome-wide polygenic scores were significantly associated with alcohol outcomes in an independent sample. Conclusions : These results robustly identify genetic risk for alcohol use outcomes at the variant level and in aggregate. We confirm prior evidence that genetic variation in GRID1 impacts alcohol use, and identify novel loci of interest for multiple alcohol outcomes in emerging adults. These findings indicate that genetic variation influencing normative and problematic alcohol use is, to some extent, convergent across ancestry groups. Studying college populations represents a promising avenue by which to obtain large, diverse samples for gene identification.