Additive Contributions of Polygenic Risk Scores and Interpersonal Stressors to Adolescent Body Mass Index.

Objective: Genetics contributes to elevated body mass index (BMI) in youth. Adolescents experiencing interpersonal stressors (eg, peer victimization or parental criticism) may additionally be at a heightened risk for developing high BMI. However, few studies have examined the additive contributions of genetic factors and interpersonal stressors to BMI.

Robust inference and widespread genetic correlates from a large-scale genetic association study of human personality.

Personality traits describe stable differences in how individuals think, feel, and behave and how they interact with and experience their social and physical environments. We assemble data from 46 cohorts including 611K-1.14M participants with European-like and African-like genomes for genome-wide association studies (GWAS) of the Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism, and openness to experience), and data from 51K participants for within-family GWAS.

An Updated Polygenic Index Repository: Expanded Phenotypes, New Cohorts, and Improved Causal Inference.

Polygenic indexes (PGIs) - DNA-based phenotype predictors for individual phenotypes - have become essential tools across the biomedical and social sciences. We introduce Version 2 of the Polygenic Index Repository, which expands the number of phenotypes from 47 to 61, increases the number of participating datasets from 11 to 20, and adopts a more consistent and improved methodology for PGI construction. For 16 phenotypes, we leverage summary statistics from an updated GWAS meta-analysis with greater statistical power compared to the original release, thereby improving the PGI's predictive power.

Associations between polygenic risk scores for cardiometabolic phenotypes and adolescent depression and body dissatisfaction.

Background: Adolescents with elevated body mass index (BMI) are at an increased risk for depression and body dissatisfaction. Type 2 diabetes (T2D) is an established risk factor for depression. However, shared genetic risk between cardiometabolic conditions and mental health outcomes remains understudied in youth.

Examining the relationship between genetic risk for depression and youth episodic stress exposure.

Background: Offspring of depressed mothers have elevated risk of developing depression because they are exposed to greater stress. While generally assumed that youth's increased exposure to stress is due to the environmental effects of living with a depressed parent, youth's genes may influence stress exposure through gene-environment correlations (rGEs). To understand the relationship between risk for depression and stress, we examined the effects of polygenic risk for depression on youth stress exposure.

General . specific vulnerabilities: polygenic risk scores and higher-order psychopathology dimensions in the Adolescent Brain Cognitive Development (ABCD) Study.

Background: Polygenic risk scores (PRSs) capture genetic vulnerability to psychiatric conditions. However, PRSs are often associated with multiple mental health problems in children, complicating their use in research and clinical practice. The current study is the first to systematically test which PRSs associate broadly with all forms of childhood psychopathology, and which PRSs are more specific to one or a handful of forms of psychopathology.

Polygenic risk scores for asthma and allergic disease associate with COVID-19 severity in 9/11 responders.

Background: Genetic factors contribute to individual differences in the severity of coronavirus disease 2019 (COVID-19). A portion of genetic predisposition can be captured using polygenic risk scores (PRS). Relatively little is known about the associations between PRS and COVID-19 severity or post-acute COVID-19 in community-dwelling individuals.

TwinEQTL: ultrafast and powerful association analysis for eQTL and GWAS in twin studies.

We develop a computationally efficient alternative, TwinEQTL, to a linear mixed-effects model for twin genome-wide association study data. Instead of analyzing all twin samples together with linear mixed-effects model, TwinEQTL first splits twin samples into 2 independent groups on which multiple linear regression analysis can be validly performed separately, followed by an appropriate meta-analysis-like approach to combine the 2 nonindependent test results. Through mathematical derivations, we prove the validity of TwinEQTL algorithm and show that the correlation between 2 dependent test statistics at each single-nucleotide polymorphism is independent of its minor allele frequency.

The benefit of diagnostic whole genome sequencing in schizophrenia and other psychotic disorders.

Schizophrenia has a multifactorial etiology, involving a polygenic architecture. The potential benefit of whole genome sequencing (WGS) in schizophrenia and other psychotic disorders is not well studied. We investigated the yield of clinical WGS analysis in 251 families with a proband diagnosed with schizophrenia (N = 190), schizoaffective disorder (N = 49), or other conditions involving psychosis (N = 48).

Polygenic prediction of PTSD trajectories in 9/11 responders.

Background: Genetics hold promise of predicting long-term post-traumatic stress disorder (PTSD) outcomes following trauma. The aim of the current study was to test whether six hypothesized polygenic risk scores (PRSs) developed to capture genetic vulnerability to psychiatric conditions prospectively predict PTSD onset, severity, and 18-year course after trauma exposure.

Methods: Participants were 1490 responders to the World Trade Center (WTC) disaster (mean age at 9/11 = 38.