A5062131183- Genetic Associations and Epidemiology
- Health Systems, Economic Evaluations, Quality of Life
- Genetic Mapping and Diversity in Plants and Animals
- Genetic and phenotypic traits in livestock
- Advanced Causal Inference Techniques
- Intergenerational and Educational Inequality Studies
- Liver Disease Diagnosis and Treatment
- Autism Spectrum Disorder Research
- Cystic Fibrosis Research Advances
- Health disparities and outcomes
- Birth, Development, and Health
- Genomic variations and chromosomal abnormalities
- Pediatric health and respiratory diseases
- Cancer-related molecular mechanisms research
- Family Support in Illness
- Statistical Methods and Inference
- Software Testing and Debugging Techniques
- Resilience and Mental Health
- Iron Metabolism and Disorders
- Software System Performance and Reliability
- Child Nutrition and Feeding Issues
- Tendon Structure and Treatment
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
University of Wisconsin–Madison
2019-2025
Abstract Polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of Europeans are known to have substantially reduced predictive accuracy in non-European populations, limiting their clinical utility and raising concerns about health disparities across ancestral populations. Here, we introduce a statistical framework named X-Wing improve performance ancestrally diverse quantifies local genetic correlations for complex traits between employs an annotation-dependent...
Significance It has been shown that human genomes can affect phenotype both directly (through inherited genetic variants) and indirectly parents the family environment they create). Due to correlation between parental offspring genotypes, a standard genome-wide association study (GWAS) captures direct indirect effects. In this study, we introduce statistical framework named DONUTS estimate effects using summary statistics from GWAS conducted on own phenotypes. requires only as input, allows...
Polygenic risk scores (PRSs) have wide applications in human genetics research, but often include tuning parameters which are difficult to optimize practice due limited access individual-level data. Here, we introduce PUMAS, a novel method fine-tune PRS models using summary statistics from genome-wide association studies (GWASs). Through extensive simulations, external validations, and analysis of 65 traits, demonstrate that PUMAS can perform various model-tuning procedures GWAS effectively...
Abstract The integration of genetic data within large-scale social and health surveys provides new opportunities to test long-standing theories parental investments in children within-family inequality. Genetic predictors, called polygenic scores, allow novel assessments young children's abilities that are uncontaminated by investments, family-based samples indirect tests whether reinforced or compensated. We use over 16,000 sibling pairs from the UK Biobank relative ranking siblings’ scores...
Polygenic risk score (PRS) is a major research topic in human genetics. However, significant gap exists between PRS methodology and applications practice due to often unavailable individual-level data for various tasks including model fine-tuning, benchmarking, ensemble learning.
Ensemble learning has been increasingly popular for boosting the predictive power of polygenic risk scores (PRS), with almost every recent multi-ancestry PRS approach employing ensemble as a final step. Existing approaches rely on individual-level data model training, which severely limits their real-world applications, especially in non-European populations without sufficient genomic samples. Here, we introduce statistical framework to construct regularized PRS, allows us combine large...
Abstract The integration of genetic data within large-scale social and health surveys provides new opportunities to test long standing theories parental investments in children within-family inequality. Genetic predictors, called polygenic scores, allow novel assessments young children’s abilities that are uncontaminated by investments, family-based samples indirect tests whether reinforced or compensated. We use over 16,000 sibling pairs from the UK Biobank relative ranking siblings’ scores...
Abstract Background Although respiratory pathology is known to develop in young children with cystic fibrosis (CF), the determinants of early‐onset lung disease have not been elucidated. Objective We aimed determine impact potential intrinsic and extrinsic risk factors during first 3 years life, testing hypothesis that both contribute significantly CF disease. Design studied 104 infants born 2012–2017, diagnosed through newborn screening by age months, evaluated comprehensively 36 months...
Abstract Polygenic risk scores (PRSs) have wide applications in human genetics research. Notably, most PRS models include tuning parameters which improve predictive performance when properly selected. However, existing model-tuning methods require individual-level genetic data as the training dataset or a validation independent from both and testing samples. These rarely exist practice, creating significant gap between methodology applications. Here, we introduce PUMAS (Parameter-tuning...
Epidemiologic associations estimated from observational data are often confounded by genetics due to pervasive pleiotropy among complex traits. Many studies either neglect genetic confounding altogether or rely on adjusting for polygenic scores (PGS) in regression analysis. In this study, we unveil that the commonly employed PGS approach is inadequate removing measurement error and model misspecification. To tackle challenge, introduce PENGUIN, a principled framework control based variance...
Epidemiologic associations estimated from observational data are often confounded by genetics due to pervasive pleiotropy among complex traits. Many studies either neglect genetic confounding altogether or rely on adjusting for polygenic scores (PGS) in regression analysis. In this study, we unveil that the commonly employed PGS approach is inadequate removing measurement error and model misspecification. To tackle challenge, introduce PENGUIN, a principled framework control based variance...
Abstract Polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of Europeans are known to have substantially reduced predictive accuracy in non-European populations, limiting its clinical utility and raising concerns about health disparities across ancestral populations. Here, we introduce a novel statistical framework named X-Wing improve performance ancestrally diverse quantifies local genetic correlations for complex traits between employs annotation-dependent...
Abstract Marginal effect estimates in genome-wide association studies (GWAS) are mixtures of direct and indirect genetic effects. Existing methods to dissect these effects require family-based, individual-level phenotypic data with large samples, which is difficult obtain practice. Here, we propose a novel statistical framework estimate using summary statistics from GWAS conducted on own offspring phenotypes. Applied birth weight, our method showed nearly identical results those obtained...
Background Polygenic risk score (PRS) is a major research topic in human genetics. However, significant gap exists between PRS methodology and applications practice due to often unavailable individual-level data for various tasks including model fine-tuning, benchmarking, ensemble learning. Results We introduce an innovative statistical framework optimize benchmark models using summary statistics of genome-wide association studies. This builds upon our previous work can fine-tune virtually...
Background Polygenic risk score (PRS) derived from summary statistics of genome‐wide association studies (GWAS) is a useful tool to infer an individual’s genetic for health outcomes and has gained increasing popularity in human genetics research. PRS its simplest form enjoys both computational efficiency easy accessibility, yet the predictive performance remains moderate diseases traits. Results We provide overview recent advances statistical methods improve PRS’s by incorporating...
Abstract Background Previously, we developed a co‐calibrated and harmonized brain pathology score (BPS) across prospective cohort studies with research donation that incorporates multiple forms of postmortem neuropathology, using confirmatory factor analysis. We sought to identify genetic loci associated BPS systems‐biology approach, combining data from participants in the Adult Changes Thought (ACT), Religious Orders Study, Rush Memory Aging Project (ROSMAP) autopsy cohorts. Method used...
Abstract Polygenic risk scores (PRS) derived from summary statistics of genome-wide association studies (GWAS) have enjoyed great popularity in human genetics research. Applied to population cohorts, PRS can effectively stratify individuals by group and has promising applications early diagnosis clinical intervention. However, our understanding within-family polygenic is incomplete, part because the small samples per family significantly limits power. Here, address this challenge, we...
Importance Many psychiatric outcomes share a common etiologic pathway reflecting behavioral disinhibition, generally referred to as externalizing (EXT) disorders. Recent genome-wide association studies (GWASs) have demonstrated the overlap between EXT disorders and important aspects of veterans’ health, such suicide-related behaviors substance use (SUDs). Objective To explore correlates risk for within Veterans Health Administration (VA) Million Veteran Program (MVP). Design, Setting,...
The current study evaluates genetic heterogeneities in response to trauma among U.S. young adults. Using Add Health Wave III, which coincidently overlapped with the September 11 attacks, and a depression mean variance polygenic scores, we investigate how scores moderate causal effect of 9/11 on mental health. Our results show presence heterogeneity, where those high plasticity experience an increase depressive symptoms following while low do not. While documented differences reactions are...
Redundancy-based automated program repair (APR), which generates patches by referencing existing source code, has gained much attention since they are effective in repairing real-world bugs with good interpretability. However, approaches either demand the existence of multi-line similar code or randomly reference can only a small number many incorrect patches, hindering their wide application practice. In this work, we aim to improve effectiveness redundancy-based APR exploring more reuse...