Publications by authors named "P Bronson"
Background And Objectives: Multiple sclerosis (MS) age at onset (AAO) is a clinical predictor of long-term disease outcomes, independent of disease duration. Little is known about the genetic and biological mechanisms underlying age of first symptoms. We conducted a genome-wide association study (GWAS) to investigate associations between individual genetic variation and the MS AAO phenotype.
View Article and Find Full Text PDFWhile the genetics of MS risk susceptibility are well-described, and recent progress has been made on the genetics of disease severity, the genetics of disease progression remain elusive. We therefore investigated the genetic determinants of MS progression on longitudinal brain MRI: change in brain volume (BV) and change in T2 lesion volume (T2LV), reflecting progressive tissue loss and increasing disease burden, respectively. We performed genome-wide association studies of change in BV (N = 3401) and change in T2LV (N = 3513) across six randomized clinical trials from Biogen and Roche/Genentech: ADVANCE, ASCEND, DECIDE, OPERA I & II, and ORATORIO.
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- Human genetic variation has helped identify key regulators of hemoglobin switching, notably BCL11A, leading to therapeutic advancements, but understanding of the broader regulatory mechanisms remains limited.
- A large genome-wide association study involving 28,279 individuals from 5 continents identified 178 significant genetic variants affecting fetal hemoglobin regulation.
- The research pinpointed BACH2 as a new regulator and clarified how certain genetic variations, including rare deletions, interact to influence fetal hemoglobin levels, paving the way for improved treatments for conditions like sickle cell disease and β-thalassemia.
Article Synopsis
- Genome-wide association studies have identified many common genetic variants tied to human diseases, but the exploration of rare genetic variations has been limited.
- This study analyzes exome-sequencing data from 394,841 individuals in the UK Biobank to assess the impact of rare coding variations across 4,529 phenotypes, linking genetic associations to their frequency and potential harmfulness.
- The findings contribute to our understanding of genetic factors in health and disease, offering a public dataset and tools like the Genebass browser for researchers to investigate rare variant associations.
Stroke is the second leading cause of death with substantial unmet therapeutic needs. To identify potential stroke therapeutic targets, we estimate the causal effects of 308 plasma proteins on stroke outcomes in a two-sample Mendelian randomization framework and assess mediation effects by stroke risk factors. We find associations between genetically predicted plasma levels of six proteins and stroke (P ≤ 1.
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