Browsing by Subject "Gene‐environment interaction"

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    Family environment and polygenic risk in the bipolar high-risk context
    (Wiley, 2023-03-16) Stapp, Emma K.; Fullerton, Janice M.; Musci, Rashelle J.; Zandi, Peter P.; McInnis, Melvin G.; Mitchell, Philip B.; Hulvershorn, Leslie A.; Ghaziuddin, Neera; Roberts, Gloria; Ferrera, Alessandra G.; Nurnberger, John I.; Wilcox, Holly C.; Psychiatry, School of Medicine
    Background: The interaction of polygenic risk (PRS) and environmental effects on development of bipolar disorder (BD) is understudied, as are high-risk offspring perceptions of their family environment (FE). We tested the association of offspring-perceived FE in interaction with BD-PRS on liability for BD in offspring at high or low familial risk for BD. Methods: Offspring of a parent with BD (oBD; n = 266) or no psychiatric disorders (n = 174), aged 12-21 at recruitment, participated in the US and Australia. Empirically-derived profiles of FE classified offspring by their perceived levels of familial cohesion, flexibility, and conflict. Offspring BD-PRS were derived from Psychiatric Genomics Consortium BD-GWAS. Lifetime DSM-IV bipolar disorders were derived from the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. We used a novel stepwise approach for latent class modeling with predictors and distal outcomes. Results: Fifty-two offspring were diagnosed with BD. For those with well-functioning FE (two-thirds of the sample), higher BD-PRS tracked positively with liability for BD. However, for those with high-conflict FEs, the relationship between BD-PRS and liability to BD was negative, with highest risk for BD observed with lower BD-PRS. In exploratory analyses, European-ancestry offspring with BD had elevated history of suicidal ideation in high-conflict FE compared to well-functioning-FE, and of suicide attempt with low-BD-PRS and high-conflict FE. Conclusions: The data suggest that the relationship of BD-PRS and offspring liability for BD differed between well-functioning versus high-conflict FE, potentially in line with a multifactorial liability threshold model and supporting future study of and interventions improving family dynamics.
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    Multivariate partial linear varying coefficients model for gene‐environment interactions with multiple longitudinal traits
    (Wiley, 2022) Wang, Honglang; Zhang, Jingyi; Klump, Kelly L.; Burt, Sybil Alexandra; Cui, Yuehua; Mathematical Sciences, School of Science
    Correlated phenotypes often share common genetic determinants. Thus, a multi‐trait analysis can potentially increase association power and help in understanding pleiotropic effect. When multiple traits are jointly measured over time, the correlation information between multivariate longitudinal responses can help to gain power in association analysis, and the longitudinal traits can provide insights on the dynamic gene effect over time. In this work, we propose a multivariate partially linear varying coefficients model to identify genetic variants with their effects potentially modified by environmental factors. We derive a testing framework to jointly test the association of genetic factors and illustrated with a bivariate phenotypic trait, while taking the time varying genetic effects into account. We extend the quadratic inference functions to deal with the longitudinal correlations and used penalized splines for the approximation of nonparametric coefficient functions. Theoretical results such as consistency and asymptotic normality of the estimates are established. The performance of the testing procedure is evaluated through Monte Carlo simulation studies. The utility of the method is demonstrated with a real data set from the Twin Study of Hormones and Behavior across the menstrual cycle project, in which single nucleotide polymorphisms associated with emotional eating behavior are identified.