scholarly journals Sibling Differences in Educational Polygenic Scores: How Do Parents React?

2019 ◽  
Author(s):  
Anna Sanz‐de‐Galdeano ◽  
Anastasia Terskaya
Keyword(s):  
Polygenic Scores ◽  
Sibling Differences

240-OR: Combining Type 2 Diabetes Polygenic Scores Improves Prediction in 36,000 European and Non-European Participants in the Partners Healthcare Biobank

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 240-OR
Author(s):  
JOSEP M. MERCADER ◽  
JOSE C. FLOREZ ◽  
AARON LEONG ◽  
VARINDERPAL KAUR ◽  
MIRIAM UDLER ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Polygenic Scores

Polygenic Scores Predict the Development of Alcohol and Nicotine Use Problems from Adolescence through Young Adulthood

2020 ◽  
Author(s):  
Joseph D. Deak ◽  
D. Angus Clark ◽  
Mengzhen Liu ◽  
C. Emily Durbin ◽  
William G. Iacono ◽  
...  
Keyword(s):  
Substance Use ◽  
Alcohol Use ◽  
Young Adulthood ◽  
Externalizing Behavior ◽  
Molecular Genetic ◽  
Early Adulthood ◽  
Predictive Utility ◽  
Problematic Use ◽  
Discovery Sample ◽  
Polygenic Scores

Objective: Molecular genetic studies of alcohol and nicotine have identified many genome-wide loci. We examined the predictive utility of drinking and smoking polygenic scores (PGS) for alcohol and nicotine use from late childhood to early adulthood, substance-specific versus broader-liability PGS effects, and if PGS performance varied between consumption versus pathological use. Methods: Latent growth curve models with structured residuals were used to assess the predictive utility of drinks per week and regular smoking PGS for measures of alcohol and nicotine consumption and problematic use from age 14 to 34. PGSs were generated from the largest discovery sample for alcohol and nicotine use to date (i.e., GSCAN), and examined for associations with alcohol and nicotine use in the Minnesota Twin Family Study (N=3225).Results: The drinking PGS was a significant predictor of age 14 problematic alcohol use and increases in problematic use during young adulthood. The smoking PGS was a significant predictor for all nicotine use outcomes. After adjusting for the effects of both PGSs, the smoking PGS demonstrated incremental predictive utility for most alcohol use outcomes and remained a significant predictor of nicotine use trajectories. Conclusions: Higher PGS for drinking and smoking were associated with more problematic levels of substance use longitudinally. The smoking PGS seems to capture both nicotine-specific and non-specific genetic liability for substance use, and may index genetic risk for broader externalizing behavior. Validation of PGS within longitudinal designs may have important clinical implications should future studies support the clinical utility of PGS for substance use disorders.

Contrasting Broad- and Clinically- defined Polygenic Indicators of Depression and Depression-related Phenotypes in Adults and Children

2020 ◽  
Author(s):  
John E. McGeary ◽  
Chelsie Benca-Bachman ◽  
Victoria Risner ◽  
Christopher G Beevers ◽  
Brandon Gibb ◽  
...  
Keyword(s):  
Suicidal Ideation ◽  
Cognitive Reappraisal ◽  
Twin Studies ◽  
European Ancestry ◽  
Summary Statistics ◽  
Depression Severity ◽  
Uk Biobank ◽  
Polygenic Scores ◽  
Adults And Children ◽  
The Uk

Twin studies indicate that 30-40% of the disease liability for depression can be attributed to genetic differences. Here, we assess the explanatory ability of polygenic scores (PGS) based on broad- (PGSBD) and clinical- (PGSMDD) depression summary statistics from the UK Biobank using independent cohorts of adults (N=210; 100% European Ancestry) and children (N=728; 70% European Ancestry) who have been extensively phenotyped for depression and related neurocognitive phenotypes. PGS associations with depression severity and diagnosis were generally modest, and larger in adults than children. Polygenic prediction of depression-related phenotypes was mixed and varied by PGS. Higher PGSBD, in adults, was associated with a higher likelihood of having suicidal ideation, increased brooding and anhedonia, and lower levels of cognitive reappraisal; PGSMDD was positively associated with brooding and negatively related to cognitive reappraisal. Overall, PGS based on both broad and clinical depression phenotypes have modest utility in adult and child samples of depression.

Developmental milestones in early childhood and genetic liability to neurodevelopmental disorders

2020 ◽  
Author(s):  
Laurie John Hannigan ◽  
Ragna Bugge Askeland ◽  
Helga Ask ◽  
Martin Tesli ◽  
Elizabeth Corfield ◽  
...  
Keyword(s):  
Language Development ◽  
Motor Development ◽  
Neurodevelopmental Disorders ◽  
Autism Spectrum ◽  
Probit Regression ◽  
Developmental Milestones ◽  
Genetic Liability ◽  
Polygenic Scores ◽  
Walking Age ◽  
Children First

BackgroundEarly developmental milestones, such as the age at first walking or talking, are associated with later diagnoses of neurodevelopmental disorders, but the relationship to genetic risk for neurodevelopmental disorders are unknown. Here, we investigate associations between genetic liability to autism spectrum disorder (autism), attention deficit hyperactivity disorder (ADHD), and schizophrenia and attainment of early-life language and motor development milestones.MethodsWe use data from a genotyped sub-set (N = 15 205) of children in the Norwegian Mother, Father and Child Cohort Study (MoBa). In this sample, we calculate polygenic scores for autism; ADHD and schizophrenia and predict maternal reports of children’s age at first walking and talking, motor delays at 18 months, language delays at 3 years, and a generalized measure of concerns about development. We use linear and probit regression models in a multi-group framework to test for sex differences.ResultsADHD polygenic scores predicted earlier walking age in both males and females (β=-0.037, pFDR=0.001), and earlier first use of sentences (β=-0.087, pFDR=0.032) but delayed language development at 3 years in females only (β=0.194, pFDR=0.001). Additionally, we found evidence that autism polygenic scores were associated with later walking (β=0.027, pFDR=0.024) and motor delays at 18 months (β = 0.065, pFDR=0.028). Schizophrenia polygenic scores were associated with a measure of general concerns about development at 3 years in females only (β=0.132, pFDR=0.024).ConclusionsGenetic liabilities for neurodevelopmental disorders show some specific associations with measures of early motor and language development in the general population, including the age at which children first walk and talk. Associations are generally small and occasionally in unexpected directions. Sex differences are evident in some instances, but clear patterns across different polygenic scores and outcomes are hard to discern. These findings suggest that genetic susceptibility for neurodevelopmental disorders is manifested in the timing of developmental milestones in infancy.

Sibling Models, Categorical Outcomes, and the Intra-Class Correlation

2021 ◽  
Author(s):  
Richard Breen ◽  
John Ermisch
Keyword(s):  
Random Effects ◽  
Probability Model ◽  
Intraclass Correlation ◽  
Linear Probability Model ◽  
Intra Class Correlation ◽  
Sibling Differences ◽  
Sibling Models ◽  
Alternative Measures ◽  
Linear Probability ◽  
Parametric Estimate

Abstract In sibling models with categorical outcomes the question arises of how best to calculate the intraclass correlation, ICC. We show that, for this purpose, the random effects linear probability model is preferable to a random effects non-linear probability model, such as a logit or probit. This is because, for a binary outcome, the ICC derived from a random effects linear probability model is a non-parametric estimate of the ICC, equivalent to a statistic called Cohen’s κ. Furthermore, because κ can be calculated when the outcome has more than two categories, we can use the random effects linear probability model to compute a single ICC in cases with more than two outcome categories. Lastly, ICCs are often compared between groups to show the degree to which sibling differences vary between groups: we show that when the outcome is categorical these comparisons are invalid. We suggest alternative measures for this purpose.

scholarly journals The Genetic Basis of Hypertriglyceridemia

2021 ◽  
Vol 23 (8) ◽  
Author(s):  
Germán D. Carrasquilla ◽  
Malene Revsbech Christiansen ◽  
Tuomas O. Kilpeläinen
Keyword(s):  
Genetic Basis ◽  
Association Studies ◽  
Cumulative Effect ◽  
Genome Wide Association Studies ◽  
Genetic Loci ◽  
Risk Variants ◽  
Genome Wide ◽  
Severe Hypertriglyceridemia ◽  
Increased Risk ◽  
Polygenic Scores

Abstract Purpose of Review Hypertriglyceridemia is a common dyslipidemia associated with an increased risk of cardiovascular disease and pancreatitis. Severe hypertriglyceridemia may sometimes be a monogenic condition. However, in the vast majority of patients, hypertriglyceridemia is due to the cumulative effect of multiple genetic risk variants along with lifestyle factors, medications, and disease conditions that elevate triglyceride levels. In this review, we will summarize recent progress in the understanding of the genetic basis of hypertriglyceridemia. Recent Findings More than 300 genetic loci have been identified for association with triglyceride levels in large genome-wide association studies. Studies combining the loci into polygenic scores have demonstrated that some hypertriglyceridemia phenotypes previously attributed to monogenic inheritance have a polygenic basis. The new genetic discoveries have opened avenues for the development of more effective triglyceride-lowering treatments and raised interest towards genetic screening and tailored treatments against hypertriglyceridemia. Summary The discovery of multiple genetic loci associated with elevated triglyceride levels has led to improved understanding of the genetic basis of hypertriglyceridemia and opened new translational opportunities.

scholarly journals A microRNA panel compared to environmental and polygenic scores for colorectal cancer risk prediction

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Janhavi R. Raut ◽  
Ben Schöttker ◽  
Bernd Holleczek ◽  
Feng Guo ◽  
Megha Bhardwaj ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Prediction ◽  
Risk Score ◽  
Characteristic Curve ◽  
Predictive Ability ◽  
Population Based ◽  
Polygenic Risk Score ◽  
Nucleotide Polymorphisms ◽  
Polygenic Scores

AbstractCirculating microRNAs (miRNAs) could improve colorectal cancer (CRC) risk prediction. Here, we derive a blood-based miRNA panel and evaluate its ability to predict CRC occurrence in a population-based cohort of adults aged 50–75 years. Forty-one miRNAs are preselected from independent studies and measured by quantitative-real-time-polymerase-chain-reaction in serum collected at baseline of 198 participants who develop CRC during 14 years of follow-up and 178 randomly selected controls. A 7-miRNA score is derived by logistic regression. Its predictive ability, quantified by the optimism-corrected area-under-the-receiver-operating-characteristic-curve (AUC) using .632+ bootstrap is 0.794. Predictive ability is compared to that of an environmental risk score (ERS) based on known risk factors and a polygenic risk score (PRS) based on 140 previously identified single-nucleotide-polymorphisms. In participants with all scores available, optimism-corrected-AUC is 0.802 for the 7-miRNA score, while AUC (95% CI) is 0.557 (0.498–0.616) for the ERS and 0.622 (0.564–0.681) for the PRS.

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