Brooke N. Wolford
A5091351708- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Aortic aneurysm repair treatments
- Aortic Disease and Treatment Approaches
- Bioinformatics and Genomic Networks
- Connective tissue disorders research
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Genetic Mapping and Diversity in Plants and Animals
- SARS-CoV-2 and COVID-19 Research
- Liver Disease Diagnosis and Treatment
- Genetics and Physical Performance
- Genetic and phenotypic traits in livestock
- Cancer-related gene regulation
- Folate and B Vitamins Research
- Cardiomyopathy and Myosin Studies
- Biomedical Text Mining and Ontologies
- Pancreatic function and diabetes
- Cardiovascular Health and Risk Factors
- RNA Research and Splicing
- Venous Thromboembolism Diagnosis and Management
- interferon and immune responses
- Thyroid Disorders and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- BRCA gene mutations in cancer
Norwegian University of Science and Technology
2021-2025
University of Michigan
2017-2023
Michigan Medicine
2018-2022
Brooke
2018-2022
Washtenaw Community College
2020
Michigan United
2018
National Human Genome Research Institute
2016-2018
National Institutes of Health
2016-2017
Genome-wide association studies (GWAS) have identified >100 independent SNPs that modulate the risk of type 2 diabetes (T2D) and related traits. However, pathogenic mechanisms most these remain elusive. Here, we examined genomic, epigenomic, transcriptomic profiles in human pancreatic islets to understand links between genetic variation, chromatin landscape, gene expression context T2D. We first integrated genome transcriptome variation across 112 islet samples produce dense cis-expression...
Polygenic risk scores (PRSs) have been widely explored in precision medicine. However, few studies thoroughly investigated their best practices global populations across different diseases. We here utilized data from Global Biobank Meta-analysis Initiative (GBMI) to explore methodological considerations and PRS performance 9 biobanks for 14 disease endpoints. Specifically, we constructed PRSs using pruning thresholding (P + T) PRS-continuous shrinkage (CS). For both methods, a European-based...
Abstract Type 2 diabetes (T2D) results from the combined effects of genetic and environmental factors on multiple tissues over time. Of >100 variants associated with T2D related traits in genome-wide association studies (GWAS), >90% occur non-coding regions, suggesting a strong regulatory component to risk. Here understand how status, metabolic variation influence gene expression, we analyse skeletal muscle biopsies 271 well-phenotyped Finnish participants glucose tolerance ranging...
Abstract Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. To better understand the genetic contribution to TSH levels, we conduct a GWAS meta-analysis at 22.4 million markers in up 119,715 individuals identify 74 genome-wide significant loci TSH, of which 28 are previously unreported. Functional experiments show that thyroglobulin protein-altering variants P118L G67S impact secretion. Phenome-wide association analysis UK Biobank demonstrates pleiotropic...
Abdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality; however, its genetic determinants remain incompletely defined. In total, 10 previously identified risk loci explain a small fraction AAA heritability.We performed genome-wide association study in the Million Veteran Program testing ≈18 million DNA sequence variants with (7642 cases and 172 controls) veterans European ancestry independent replication up to 4972 99 858 controls. We then used mendelian...
Background: Venous thromboembolism (VTE) is a life-threatening vascular event with environmental and genetic determinants. Recent VTE genome-wide association studies (GWAS) meta-analyses involved nearly 30 000 cases identified up to 40 loci associated risk, including not previously suspected play role in hemostasis. The aim of our research was expand discovery new by using cross-ancestry genomic resources. Methods: We present meta-analyzed GWAS results involving 81 669 from studies,...
Abstract Polygenic scores (PGSs) offer the ability to predict genetic risk for complex diseases across life course; a key benefit over short-term prediction models. To produce estimates relevant clinical and public health decision-making, it is important account varying effects due age sex. Here, we develop novel framework estimate country-, age-, sex-specific of cumulative incidence stratified by PGS 18 high-burden diseases. We integrate associations from seven studies in four countries ( N...
Background: Thoracic aortic dissection is an emergent life-threatening condition. Routine screening for genetic variants causing thoracic not currently performed patients or family members. Methods: We whole exome sequencing of 240 with (n=235) rupture (n=5) and 258 controls matched age, sex, ancestry. Blinded to case-control status, we annotated in 11 genes pathogenicity. Results: Twenty-four pathogenic 6 (COL3A1, FBN1, LOX, PRKG1, SMAD3, TGFBR2) were identified 26 individuals, representing...
Abstract Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses participants in HUNT Study Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related disease, but detrimental function. We 76 (11 previously unreported) presumed causal...
Summary Biobanks are being established across the world to understand genetic, environmental, and epidemiological basis of human diseases with goal better prevention treatments. Genome-wide association studies (GWAS) have been very successful at mapping genomic loci for a wide range traits, but in general, lack appropriate representation diverse ancestries - most biobanks preceding GWAS composed individuals European ancestries. Here, we introduce Global Biobank Meta-analysis Initiative...
Molecular mechanisms remain unknown for most type 2 diabetes genome-wide association study identified loci. Variants associated with and fasting glucose levels reside in introns of ADCY5, a gene that encodes adenylate cyclase 5. Adenylate 5 catalyzes the production cyclic AMP, which is second messenger molecule involved cell signaling pancreatic β-cell insulin secretion. We demonstrated risk alleles are decreased ADCY5 expression human islets examined candidate variants regulatory function....