scholarly journals Predicting substance use in emerging adulthood: A genetically informed study of developmental transactions between impulsivity and family conflict

2016 ◽  
Vol 28 (3) ◽  
pp. 673-688 ◽  
Author(s):  
Kit K. Elam ◽  
Frances L. Wang ◽  
Kaitlin Bountress ◽  
Laurie Chassin ◽  
Danielle Pandika ◽  
...  
Keyword(s):  
Substance Use ◽  
Emerging Adulthood ◽  
Middle Childhood ◽  
Family Conflict ◽  
Risk Scores ◽  
Family Risk Factors ◽  
Family Risk ◽  
Mothers And Fathers ◽  
Polygenic Risk ◽  
Increased Risk

AbstractDeviance proneness models propose a multilevel interplay in which transactions among genetic, individual, and family risk factors place children at increased risk for substance use. We examined bidirectional transactions between impulsivity and family conflict from middle childhood to adolescence and their contributions to substance use in adolescence and emerging adulthood (n = 380). Moreover, we examined children's, mothers’, and fathers’ polygenic risk scores for behavioral undercontrol, and mothers’ and fathers’ interparental conflict and substance disorder diagnoses as predictors of these transactions. The results support a developmental cascade model in which children's polygenic risk scores predicted greater impulsivity in middle childhood. Impulsivity in middle childhood predicted greater family conflict in late childhood, which in turn predicted greater impulsivity in late adolescence. Adolescent impulsivity subsequently predicted greater substance use in emerging adulthood. Results are discussed with respect to evocative genotype–environment correlations within developmental cascades and applications to prevention efforts.

Association between Polygenic Risk Scores for ADHD and Asthma: A Birth Cohort Investigation

2021 ◽  
pp. 108705472110201
Author(s):  
Douglas Teixeira Leffa ◽  
Bernardo Horta ◽  
Fernando C. Barros ◽  
Ana M. B. Menezes ◽  
Thais Martins-Silva ◽  
...  
Keyword(s):  
Birth Cohort ◽  
Genetic Background ◽  
Adult Adhd ◽  
Risk Scores ◽  
Asthma Diagnosis ◽  
Polygenic Risk ◽  
Increased Risk ◽  
Genetic Overlap ◽  
Genetic Mechanisms ◽  
Shared Genetic

Objective: Shared genetic mechanisms have been hypothesized to explain the comorbidity between ADHD and asthma. To evaluate their genetic overlap, we relied on data from the 1982 Pelotas birth cohort to test the association between polygenic risk scores (PRSs) for ADHD (ADHD-PRSs) and asthma, and PRSs for asthma (asthma-PRSs) and ADHD. Method: We analyzed data collected at birth, 2, 22, and 30 years from 3,574 individuals. Results: Subjects with ADHD had increased risk of having asthma (OR 1.92, 95% CI 1.01–3.66). The association was stronger for females. Our results showed no evidence of association between ADHD-PRSs and asthma or asthma-PRSs and ADHD. However, an exploratory analysis suggested that adult ADHD might be genetically associated with asthma. Conclusion: Our results do not support a shared genetic background between both conditions. Findings should be viewed in light of important limitations, particularly the sample size and the self-reported asthma diagnosis. Studies in larger datasets are required to better explore the genetic overlap between adult ADHD and asthma.

scholarly journals Polygenic risk scores for coronary artery disease and subsequent event risk amongst established cases

2020 ◽  
Vol 29 (8) ◽  
pp. 1388-1395
Author(s):  
Laurence J Howe ◽  
Frank Dudbridge ◽  
Amand F Schmidt ◽  
Chris Finan ◽  
Spiros Denaxas ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Scores ◽  
Effect Estimate ◽  
Inverse Association ◽  
Uk Biobank ◽  
Case Control Studies ◽  
Polygenic Risk ◽  
Increased Risk ◽  
Artery Disease

Abstract Background There is growing evidence that polygenic risk scores (PRSs) can identify individuals with elevated lifetime risk of coronary artery disease (CAD). Whether they can also be used to stratify the risk of subsequent events among those surviving a first CAD event remain uncertain, with possible biological differences between CAD onset and progression, and the potential for index event bias. Methods Using two baseline subsamples of UK Biobank: prevalent CAD cases (N = 10 287) and individuals without CAD (N = 393 108), we evaluated associations between a CAD PRS and incident cardiovascular and fatal outcomes. Results A 1 SD higher PRS was associated with an increased risk of incident myocardial infarction (MI) in participants without CAD (OR 1.33; 95% CI 1.29, 1.38), but the effect estimate was markedly attenuated in those with prevalent CAD (OR 1.15; 95% CI 1.06, 1.25) and heterogeneity P = 0.0012. Additionally, among prevalent CAD cases, we found an evidence of an inverse association between the CAD PRS and risk of all-cause death (OR 0.91; 95% CI 0.85, 0.98) compared with those without CAD (OR 1.01; 95% CI 0.99, 1.03) and heterogeneity P = 0.0041. A similar inverse association was found for ischaemic stroke [prevalent CAD (OR 0.78; 95% CI 0.67, 0.90); without CAD (OR 1.09; 95% CI 1.04, 1.15), heterogeneity P < 0.001]. Conclusions Bias induced by case stratification and survival into UK Biobank may distort the associations of PRS derived from case-control studies or populations initially free of disease. Differentiating between effects of possible biases and genuine biological heterogeneity is a major challenge in disease progression research.

scholarly journals The Impact of Peer Substance Use and Polygenic Risk on Trajectories of Heavy Episodic Drinking Across Adolescence and Emerging Adulthood

2016 ◽  
Vol 41 (1) ◽  
pp. 65-75 ◽  
Author(s):  
James J. Li ◽  
Seung Bin Cho ◽  
Jessica E. Salvatore ◽  
Howard J. Edenberg ◽  
Arpana Agrawal ◽  
...  
Keyword(s):  
Substance Use ◽  
Emerging Adulthood ◽  
Heavy Episodic Drinking ◽  
Polygenic Risk ◽  
Peer Substance Use ◽  
The Impact

scholarly journals A multi-ethnic polygenic risk score is associated with hypertension prevalence and progression throughout adulthood

2021 ◽  
Author(s):  
Nuzulul Kurniansyah ◽  
Matthew O Goodman ◽  
Tanika Kelly ◽  
Tali Elfassi ◽  
Kerri Wiggins ◽  
...  
Keyword(s):  
African Americans ◽  
Clinical Outcomes ◽  
Risk Scores ◽  
Training Dataset ◽  
P Value ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Incident Hypertension ◽  
Novel Approach ◽  
Increased Risk

Background: We used summary statistics from previously-published GWAS of systolic and diastolic BP and of hypertension to construct Polygenic Risk Scores (PRS) to predict hypertension across diverse populations. Methods: We used 10,314 participants of diverse ancestry from BioMe to train trait-specific PRS. We implemented a novel approach to select one of multiple potential PRS based on the same GWAS, by optimizing the coefficient of variation across estimated PRS effect sizes in independent subsets of the training dataset. We combined the 3 selected trait-specific PRS as their unweighted sum, called "PRSsum". We evaluated PRS associations in an independent dataset of 39,035 individuals from eight cohort studies, to select the final, multi-ethnic, HTN-PRS. We estimated its association with prevalent and incident hypertension 4-6 years later. We studied hypertension development within HTN-PRS strata in a longitudinal, six-visit, longitudinal dataset of 3,087 self-identified Black and White participants from the CARDIA study. Finally, we evaluated the HTN-PRS association with clinical outcomes in 40,201 individuals from the MGB Biobank. Results: Compared to other race/ethnic backgrounds, African-Americans had higher average values of the HTN-PRS. The HTN-PRS was associated with prevalent hypertension (OR=2.10, 95% CI [1.99, 2.21], per one standard deviation (SD) of the PRS) across all participants, and in each race/ethnic background, with heterogeneity by background (p-value < 1.0x10-4). The lowest estimated effect size was in African Americans (OR=1.53, 95% CI [1.38, 1.69]). The HTN-PRS was associated with new onset hypertension among individuals with normal (respectively, elevated) BP at baseline: OR=1.71, 95% CI [1.55, 1.91] (OR=1.48, 95% CI [1.27, 1.71]). Association was further observed in age-stratified analysis. In CARDIA, Black participants with high HTN-PRS percentiles developed hypertension earlier than White participants with high HTN-PRS percentiles. The HTN-PRS was significantly associated with increased risk of coronary artery disease (OR=1.12), ischemic stroke (OR=1.15), type 2 diabetes (OR=1.19), and chronic kidney disease (OR=1.12), in the MGB Biobank. Conclusions: The multi-ethnic HTN-PRS is associated with both prevalent and incident hypertension at 4-6 years of follow up across adulthood and is associated with clinical outcomes.

scholarly journals Prenatal smoking, alcohol and caffeine exposure and ADHD risk in childhood: parental comparisons and polygenic risk score (PRS) analyses

2021 ◽  
Author(s):  
Elis Haan ◽  
Hannah M Sallis ◽  
Luisa Zuccolo ◽  
Jeremy Labrecque ◽  
Eivind Ystrom ◽  
...  
Keyword(s):  
Substance Use ◽  
Coffee Consumption ◽  
Negative Control ◽  
Sensitivity Analyses ◽  
Risk Scores ◽  
Prenatal Smoking ◽  
Polygenic Risk Score ◽  
Caffeine Consumption ◽  
Polygenic Risk ◽  
Prenatal Substance Use

Background and aims: Several studies have indicated that maternal prenatal substance use may be associated with offspring ADHD via intrauterine effects. We investigated associations between maternal prenatal smoking, alcohol and caffeine consumption with childhood ADHD risk accounting for shared familial factors. Design: First, we used a negative control design comparing maternal and paternal substance use. Three models were used for negative control analyses: unadjusted (without confounders); adjusted (including confounders) and mutually adjusted (including confounders and partners substance use). The results were meta-analysed across the cohorts. Second, we used polygenic risk scores (PRS) as proxies for exposures. Maternal PRS for genetic variants of smoking, alcohol and coffee consumption were regressed against ADHD risk. We triangulated the results across the two approaches to infer causality. Setting: We used data from three longitudinal pregnancy cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK, Generation R study (GenR) in the Netherlands and Norwegian Mother, Father and Child Cohort study (MoBa) in Norway. Participants: Phenotype data available for children was: N(ALSPAC)=7,850; N(GENR)=3,849 and N(MOBA)=43,512. Genotype data available for mothers was: N(ALSPAC)=7,074 and N(MOBA)=14,583. Measurements: Offspring ADHD risk around age 7-8 was derived by dichotomising symptom scores from multiple questionnaires and parental self-reported substance use was measured at the 2nd pregnancy trimester. Findings: The pooled estimate for maternal prenatal substance use showed an association with ADHD risk (OR_SMOKING=1.11, 95%CI 1.00-1.23; OR_ALCOHOL=1.27, 95%CI 1.08-1.49; OR_CAFFEINE=1.05, 95%CI 1.00-1.11), while not for fathers (OR_SMOKING=1.03, 95%CI 0.95-1.13; OR_ALCOHOL=0.83, 95%CI 0.47-1.48; OR_CAFFEINE=1.02, 95%CI 0.97-1.07). However, maternal associations did not persist in sensitivity analyses (substance use before pregnancy, adjustment for maternal ADHD in MoBa). The PRS analyses did not show evidence of association in ALSPAC or MoBa. Conclusions: Our results do not provide support for a causal intrauterine effect of maternal prenatal substance use on offspring attention-deficit hyperactivity disorder risk.

Association Between Polygenic Risk Score and the Progression from Mild Cognitive Impairment to Alzheimer’s Disease

2021 ◽  
pp. 1-13
Author(s):  
Hongliang Liu ◽  
Michael Lutz ◽  
Sheng Luo ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Risk Scores ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Increased Risk ◽  
Risk Of Progression ◽  
Clinical Changes

Background: Mild cognitive impairment (MCI) is a heterogeneous condition and MCI patients are at increased risk of progression to dementia due to Alzheimer’s disease (AD). Objective: In this study, we aim to evaluate the associations between polygenic risk scores (PRSs) and 1) time to AD progression from MCI, 2) changes in longitudinal cognitive impairment, and 3) biomarkers from cerebrospinal fluid and imaging. Methods: We constructed PRS by using 40 independent non-APOE SNPs from well-replicated AD GWASs and tested its association with the progression time from MCI to AD by using 767 MCI patients from the ADNI study and 1373 patients from the NACC study. PRSs calculated with other methods were also computed. Results: We found that the PRS constructed with SNPs that reached genome-wide significance predicted the progression from MCI to AD (beta = 0.182, se = 0.061, p = 0.003) after adjusting for the demographic and clinical variables. This association was replicated in the NACC dataset (beta = 0.094, se = 0.037, p = 0.009). Further analyses revealed that PRS was associated with the increased ADAS-Cog11/ADAS-Cog13/ADASQ4 scores, tau/ptau levels, and cortical amyloid burdens (PIB and AV45), but decreased hippocampus and entorhinal cortex volumes (p <  0.05). Mediation analysis showed that the effect of PRS on the increased risk of AD may be mediated by Aβ 42 (beta = 0.056, SE = 0.026, p = 0.036). Conclusion: Our findings suggest that PRS can be useful for the prediction of time to AD and other clinical changes after the diagnosis of MCI.

Discriminating bipolar depression from major depressive disorder with polygenic risk scores

2020 ◽  
pp. 1-8 ◽  
Author(s):  
David T. Liebers ◽  
Mehdi Pirooznia ◽  
Andrea Ganna ◽  
Fernando S. Goes ◽  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Clinical Features ◽  
Clinical Symptoms ◽  
Bipolar Depression ◽  
Risk Scores ◽  
Characteristic Analysis ◽  
Major Depressive ◽  
Polygenic Risk ◽  
Increased Risk

Abstract Background Although accurate differentiation between bipolar disorder (BD) and unipolar major depressive disorder (MDD) has important prognostic and therapeutic implications, the distinction is often challenging based on clinical grounds alone. In this study, we tested whether psychiatric polygenic risk scores (PRSs) improve clinically based classification models of BD v. MDD diagnosis. Methods Our sample included 843 BD and 930 MDD subjects similarly genotyped and phenotyped using the same standardized interview. We performed multivariate modeling and receiver operating characteristic analysis, testing the incremental effect of PRSs on a baseline model with clinical symptoms and features known to associate with BD compared with MDD status. Results We found a strong association between a BD diagnosis and PRSs drawn from BD (R2 = 3.5%, p = 4.94 × 10−12) and schizophrenia (R2 = 3.2%, p = 5.71 × 10−11) genome-wide association meta-analyses. Individuals with top decile BD PRS had a significantly increased risk for BD v. MDD compared with those in the lowest decile (odds ratio 3.39, confidence interval 2.19–5.25). PRSs discriminated BD v. MDD to a degree comparable with many individual symptoms and clinical features previously shown to associate with BD. When compared with the full composite model with all symptoms and clinical features PRSs provided modestly improved discriminatory ability (ΔC = 0.011, p = 6.48 × 10−4). Conclusions Our study demonstrates that psychiatric PRSs provide modest independent discrimination between BD and MDD cases, suggesting that PRSs could ultimately have utility in subjects at the extremes of the distribution and/or subjects for whom clinical symptoms are poorly measured or yet to manifest.

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