Nature Genetics, Journal Year: 2024, Volume and Issue: 56(10), P. 2093 - 2103
Published: Oct. 1, 2024
Language: Английский
Citations
2Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries
Nature Genetics, Journal Year: 2024, Volume and Issue: 56(11), P. 2333 - 2344
Published: Oct. 21, 2024
Language: Английский
Citations
2Genetic analysis of psychosis Biotypes: shared Ancestry-adjusted polygenic risk and unique genomic associations
Molecular Psychiatry, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 21, 2024
Language: Английский
Citations
2Advancing Prostate Cancer Care: Treatment Approaches to Precision Medicine, Biomarker Innovations, and Equitable Access
American Society of Clinical Oncology Educational Book, Journal Year: 2024, Volume and Issue: 44(3)
Published: May 23, 2024
Genetic testing and molecular imaging have great promise in the accurate diagnosis treatment of #prostate #cancer, but only if they can be developed implemented to achieve equitable benefit for all men.
Language: Английский
Citations
1Imputation Accuracy Across Global Human Populations
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown
Published: May 24, 2023
Abstract Genotype imputation is now fundamental for genome-wide association studies but lacks fairness due to the underrepresentation of populations with non-European ancestries. The state-of-the-art reference panel released by Trans-Omics Precision Medicine (TOPMed) initiative contains a substantial number admixed African-ancestry and Hispanic/Latino samples impute these nearly same accuracy as European-ancestry cohorts. However, primarily residing outside North America may still fall short in performance persisting underrepresentation. To illustrate this point, we curated array data from 23 publications published between 2008 2021. In total, imputed over 43k individuals across 123 around world. We identified where paled comparison that populations. For instance, mean r-squared (Rsq) 1-5% alleles Saudi Arabians (N=1061), Vietnamese (N=1264), Thai (N=2435), Papua New Guineans (N=776) were 0.79, 0.78, 0.76, 0.62, respectively. contrast, Rsq ranged 0.90 0.93 comparable European matched sample size SNP content. Outside Africa Latin America, appeared decrease genetic distances increased, predicted. Further analysis using sequencing ground truth suggested software over-estimate than populations, suggesting further disparity Using 1496 whole genome sequenced Taiwan Biobank reference, also assessed strategy improve meta-imputation, which can combine results TOPMed smaller population-specific panels. found meta-imputation design did not genome-wide. Taken together, our suggests current alternative panels, alone cannot efficacy underrepresented cohorts must ultimately strive increase diversity promote equity within genetics research.
Language: Английский
Citations
3Avoiding Liability and Other Legal Land Mines in the Evolving Genomics Landscape
Annual Review of Genomics and Human Genetics, Journal Year: 2023, Volume and Issue: 24(1), P. 333 - 346
Published: Jan. 11, 2023
This article reviews evolving legal implications for clinicians and researchers as genomics is used more widely in both the clinic translational research, reflecting rapid changes scientific knowledge well surrounding cultural political environment. Professionals will face new changing duties to make or act upon a genetic diagnosis, address direct-to-consumer testing patient care, consider health of results patients' family members, recontact patients when test change over time. Professional reproductive need be recalibrated response disruptive rights United States. We also review debate who controls flow information responsible its protection, considering globally influential European Union General Data Protection Regulation rapidly data privacy law landscape
Language: Английский
Citations
2Evaluating genomic polygenic risk scores for childhood acute lymphoblastic leukemia in Latinos
Human Genetics and Genomics Advances, Journal Year: 2023, Volume and Issue: 4(4), P. 100239 - 100239
Published: Sept. 14, 2023
The utility of polygenic risk score (PRS) models has not been comprehensively evaluated for childhood acute lymphoblastic leukemia (ALL), the most common type cancer in children. Previous PRS ALL were based on significant loci observed genome-wide association studies (GWASs), even though genomic have shown to improve prediction performance a number complex diseases. In United States, Latino (LAT) children highest ALL, but transferability LAT studied. this study, we constructed and either non-Latino White (NLW) GWAS or multi-ancestry GWAS. We found that best performed similarly between held-out NLW samples (PseudoR
Language: Английский
Citations
2Parkinson Disease Genetics Extended to African and Hispanic Ancestries in the VA Million Veteran Program
Neurology Genetics, Journal Year: 2023, Volume and Issue: 10(1)
Published: Dec. 20, 2023
Nearly all genetic analyses of Parkinson disease (PD) have been in populations European ancestry. We sought to test the ability a machine learning method extract accurate PD diagnoses from an electronic medical record (EMR) system, see whether variants identified generalize individuals African and Hispanic ancestries, compare rates across ancestries.A using natural language processing was applied EMRs US veterans participating VA Million Veteran Program (MVP) identify with PD. These putative cases were vetted via blind chart review by movement disorder specialist. A polygenic risk score (PRS) 90 established whose genotypes imputed customized Axiom Biobank Array evaluated different case groups.The EMR prediction scores had distinct trimodal distribution, 97% high group only 30% middle having credible diagnosis Using 3,542 matched 4:1 controls, PRS highly predictive ancestry (n = 3,137 cases; OR 1.82; p 8.01E-48), nearly identical effect sizes seen 184; 2.07; 3.4E-4) ancestries 221; 2.13; 3.9E-6). The much less for 2,757 who ICD code but whom lower confidence their diagnosis. No novel ancestry-specific identified. Individuals one-quarter rate compared or aged 60-70 years one half 70-80 age range. American higher proportion DNA originating Europe controls.Machine can reliably classify data large EMR. Larger studies non-European are required confirm generalizability increased coming Americans.
Language: Английский
Citations
2PRState: Incorporating genetic ancestry in prostate cancer risk scores for men of African ancestry
BMC Cancer, Journal Year: 2022, Volume and Issue: 22(1)
Published: Dec. 9, 2022
Abstract Background Prostate cancer (PrCa) is one of the most genetically driven solid cancers with heritability estimates as high 57%. Men African ancestry are at an increased risk PrCa; however, current polygenic score (PRS) models based on European groups and may not be broadly applicable. The objective this study was to construct ancestry-specific PrCa PRS (PRState) evaluate its performance. Methods group 4,533 individuals in ELLIPSE consortium used for discovery SNPs. PRState constructed weighted sum genotypes effect sizes from genome-wide association (GWAS) group. Performance evaluated using ROC-AUC analysis. Results We identified loci chromosomes 3, 8, 11 a 10 SNPs, achieving AUC 0.61 [0.60–0.63] 0.65 [0.64–0.67], when combined age family history. dropped significantly ancestry-mismatched but remained comparable trans-ancestry models. Importantly, we validated Million Veteran Program (MVP), demonstrating improved prediction metastatic ancestry. Conclusions improves MVP. This underscores need inclusion gene variant optimize PRSs identifies variants use future studies.
Language: Английский
Citations
4Different genetic architectures of complex traits and their relevance to polygenic score performance in diverse populations
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown
Published: Oct. 31, 2022
Abstract Background Despite the many insights gleaned from GWAS, polygenic predictions of complex traits have had limited success, particularly when these are applied to individuals non-European descent. A deeper understanding genetic architecture may inform why some easier predict than others. Methods Examining 163 UK Biobank, we compared and contrasted three aspects (SNP heritability, LD variability, genomic inequality) with score performance (prediction accuracy in source population, portability across populations, trait divergence populations). Here, inequality refers how unequally variance each is distributed top trait-associated SNPs, as quantified via a novel application Gini coefficients. Results Consistent reduced statistical power, binary performed worse quantitative traits. Traits low coefficients (i.e., highly architectures) include hip circumference well systolic diastolic blood pressure. large population-level differences scores skin pigmentation hair color. Focusing on 96 traits, found that heritable were more portable other ancestries. divergent distributions populations less likely predictions. Intriguingly, variability was largely uninformative regarding This suggests factors differential tagging causal SNPs drive reduction populations. Subsequent analyses identified suites similar profiles. Importantly, lifestyle psychological tended poor predictability portability. Conclusions Novel metrics capture different trait-specific architectures performance. Our findings also caution against like general happiness, alcohol frequency, average income, especially who an ancestry differs original population.
Language: Английский
Citations
3