Comparative Performance of Polygenic Risk Scores for Atherosclerotic Cardiovascular Disease Subtypes in the All of Us Research Program DOI Open Access
Johanna L. Smith, Kristján Norland, Marwan Hamed

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 5, 2024

Abstract Background Performance and portability of contemporary polygenic risk scores (PRS) for atherosclerotic cardiovascular disease (ASCVD) phenotypes vary based on different methods, training data, trait ascertainment. Objectives We aimed to investigate performance PRS ASCVD subtypes: coronary heart (CHD), abdominal aortic aneurysm (AAA), ischemic stroke (IS), peripheral artery (PAD), using the All Us Workbench which provides access a large diverse cohort with phenotype whole genome sequence data. also developed evaluated multi-trait each subtype. Methods 4 traits related factors was compared across genetic ancestry groups in 245,388 participants. Genetic EUR, African (AFR), Admixed American (AMR), remaining (combined as Other, OTH) were defined by principal components. CHD, IS, AAA, PAD, (combining well factors) assessed hazard ratios (HR) per SD increase. Results For CHD PGS003725 performed best (HR 1 increase [95% CI]), (EUR: 1.72[1.67-1.78], AFR: 1.24[1.18-1.31], AMR: 1.48[1.37-1.59], OTH: 1.65[1.52-1.79]). The performing AAA PGS003972 1.68[1.59-1.78], 1.29[1.13-1.48], 1.30[1.06-1.60], 1.45[1.20-1.75]). IS PGS000039 AFR (1.12[1.06-1.17]), AMR (1.11[1.04-1.19]), OTH (1.23[1.09-1.38]), PGS004939 EUR (1.16[1.12-1.20]). PAD PGS004940 (1.26[1.22-1.30]), (1.11[1.05-1.18]), (1.08[1.01-1.16]), (1.13[1.04-1.22]). Multi-trait better than individual phenotype. Also, derived from multi-ancestry cohorts those single ancestry. Conclusions multiple ancestrally admixed individuals. PAD.

Language: Английский

Association Between GABRG2 and Self-Rating of the Effects of Alcohol in a French Young Adult Sample DOI Creative Commons
Jenny Skumsnes Moe, Jørgen G. Bramness, Ingeborg Bolstad

et al.

Risk Management and Healthcare Policy, Journal Year: 2025, Volume and Issue: Volume 18, P. 291 - 304

Published: Jan. 1, 2025

Alcohol use is a leading risk factor for preventable death, injury, and disease globally. Low sensitivity to the effects of alcohol influenced by genes predicts harmful disorder (AUD). induces partly modulation gamma-aminobutyric acid receptors type A (GABAARs). This study investigates relationship between genetic variation in GABAAR subunit individual among French university students. The involved 1,409 students (34.5% women; mean age 20.3 years). was measured Self-Rating Effects Scale (SRE). SRE-scores from initial drinking, regular heavy drinking were investigated correlations with consumption associations single nucleotide polymorphisms (SNPs) (GABRA2, GABRG2, GABRA6). We replicated low high consumption. further found an association minor allele rs211014 (GABRG2) higher SRE-scores, linked dizziness motor incoordination. Genetic GABRG2 has previously been associated processes involving coordination (alcohol withdrawal, febrile- epileptic seizures). results our suggest that may influence sensitivity, which could inform strategies assessing AUD.

Language: Английский

Citations

0
Three Open Questions in Polygenic Score Portability DOI Creative Commons
Joyce Y. Wang,

Neeka Lin,

Michael Zietz

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 21, 2024

A major obstacle hindering the broad adoption of polygenic scores (PGS) is their lack "portability" to people that differ-in genetic ancestry or other characteristics-from GWAS samples in which effects were estimated. Here, we use UK Biobank measure change PGS prediction accuracy as a continuous function individuals' genome-wide dissimilarity sample ("genetic distance"). Our results highlight three gaps our understanding portability. First, extremely noisy at individual level and not well predicted by distance. In fact, variance explained comparably socioeconomic measures. Second, trends portability vary across traits. For several immunity-related traits, drops near zero quickly even intermediate levels This quick drop may reflect associations being more ancestry-specific traits than Third, show qualitative can depend on used. instance, for white blood cell count, (reduction mean squared error) increases with Together, cannot be understood through global groupings alone. There are other, understudied factors influencing portability, such specifics evolution trait its architecture, social context, construction score. Addressing these aid development application inform equitable genomic research.

Language: Английский

Citations

3
The PRIMED Consortium: Reducing disparities in polygenic risk assessment DOI Creative Commons
Iftikhar J. Kullo, Matthew P. Conomos, Sarah C. Nelson

et al.

The American Journal of Human Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

Citations

3
Comparative Performance of Polygenic Risk Scores for Atherosclerotic Cardiovascular Disease Subtypes in the All of Us Research Program DOI Open Access
Johanna L. Smith, Kristján Norland, Marwan Hamed

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 5, 2024

Abstract Background Performance and portability of contemporary polygenic risk scores (PRS) for atherosclerotic cardiovascular disease (ASCVD) phenotypes vary based on different methods, training data, trait ascertainment. Objectives We aimed to investigate performance PRS ASCVD subtypes: coronary heart (CHD), abdominal aortic aneurysm (AAA), ischemic stroke (IS), peripheral artery (PAD), using the All Us Workbench which provides access a large diverse cohort with phenotype whole genome sequence data. also developed evaluated multi-trait each subtype. Methods 4 traits related factors was compared across genetic ancestry groups in 245,388 participants. Genetic EUR, African (AFR), Admixed American (AMR), remaining (combined as Other, OTH) were defined by principal components. CHD, IS, AAA, PAD, (combining well factors) assessed hazard ratios (HR) per SD increase. Results For CHD PGS003725 performed best (HR 1 increase [95% CI]), (EUR: 1.72[1.67-1.78], AFR: 1.24[1.18-1.31], AMR: 1.48[1.37-1.59], OTH: 1.65[1.52-1.79]). The performing AAA PGS003972 1.68[1.59-1.78], 1.29[1.13-1.48], 1.30[1.06-1.60], 1.45[1.20-1.75]). IS PGS000039 AFR (1.12[1.06-1.17]), AMR (1.11[1.04-1.19]), OTH (1.23[1.09-1.38]), PGS004939 EUR (1.16[1.12-1.20]). PAD PGS004940 (1.26[1.22-1.30]), (1.11[1.05-1.18]), (1.08[1.01-1.16]), (1.13[1.04-1.22]). Multi-trait better than individual phenotype. Also, derived from multi-ancestry cohorts those single ancestry. Conclusions multiple ancestrally admixed individuals. PAD.

Language: Английский

Citations

0