bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Янв. 15, 2024
Abstract Androgenetic alopecia is a highly heritable trait. However, much of our understanding about the genetics male pattern baldness comes from individuals European descent. Here, we examined novel dataset comprising 2,136 men Ghana, Nigeria, Senegal, and South Africa that were genotyped using custom array. We first tested how genetic predictions generalize Europe to Africa, finding polygenic scores GWAS yielded AUC statistics ranged 0.513 0.546, indicating in African populations performed notably worse than populations. Subsequently, conducted androgenetic alopecia, focusing on self-reported patterns at age 45. After correcting for present age, population structure, study site, identified 266 moderately significant associations, 51 which independent (p-value < 10 -5 , r 2 0.2). Most associations autosomal, X chromosomes does not appear have large impact men. Finally, evolutionary causes continental differences architecture. Although Neanderthal alleles previously been associated with skin hair phenotypes, did find evidence European-ascertained hits enriched signatures ancient introgression. loci are evolving neutrally. multiple baldness-associated SNPs near EDA2R AR genes allele frequency between continents. Collectively, findings illustrate history contributes limited portability across ancestries.
Язык: Английский
Процитировано
0Genomic risk scores in prostate cancer: polygenic yes, but are they poly-ancestral?
JNCI Journal of the National Cancer Institute, Год журнала: 2024, Номер 116(5), С. 635 - 636
Опубликована: Фев. 1, 2024
There is substantial heterogeneity in the biology and clinical course of prostate cancer across patients with this diagnosis.Although most common second-leading cause cancer-related mortality American men, unlike lung, breast, or colon cancer, there are no consistent guidelines that support universal screening because risk false positives potential for overtreatment.Thus, great interest evaluating reliable biomarkers elevated risk.Polygenic scores (PRSs) a tools to improve outcomes by identifying who may benefit from more intensive monitoring therapy.Ancestry plays an important role biology, African having 64% greater developing than their European counterparts (1).Further, experience worse outcomes, earlier age presentation higher rates metastatic disease (2).Unfortunately, many stratification have been developed on ancestry cohorts not be optimal other ancestral groups (3).In issue Journal, Lee colleagues (4) examine polygenic hazard score (PHS)-specifically, PHS290-in large cohort 36 717 veterans, among whom 10 297 (28.04%) ancestry.Their investigation focuses retrospectively undergoing first biopsy, they correlate germline based subsequent positive biopsy findings.The results suggest although PHS290 associated results, it performs better (odds ratio [OR] ¼ 3.89, 95% confidence interval [CI] 3.62 4.18) those (OR 2.18, CI 1.93 2.47).PHS290 also appears diagnosing aggressive specific it.These findings congruent studies.In study Kim et al. ( 5), 3 distinct were validated sub-Saharan cohort.These included PRS269, which unique uses ancestry-specific weights; another 147marker population;
Язык: Английский
Процитировано
0Trans-Ancestry Analysis of Psychosis Biotypes: Shared Polygenic Risk and Unique Genomic Associations
Research Square (Research Square), Год журнала: 2024, Номер unknown
Опубликована: Фев. 29, 2024
Abstract The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) has categorized psychosis disorders (Schizophrenia, Schizoaffective Disorder and Bipolar Disorder) into three distinct Biotypes, based on neurobiological measurements in a multi-ancestry sample. Two recently developed post hoc ancestry adjustment methods of Polygenic Risk Scores (PRSs) generate Trans-Ancestry PRSs (TAPRSs), which allow PRS analysis samples. Applied to schizophrenia PRS, we found the Khera TAPRS method show superior portability comparable prediction accuracy as compared with Ge method. Biotypes had similar TAPRSs across ancestries. In genomic nine genes isoforms showed significant associations Transcriptome-Wide Association Study (TWAS) gene expression adult brain fetal brain, isoforms. TWAS inflation was successfully controlled by inclusion genotype Principal Components association analyses. Biotype-related diagnosis distributions differ between African American European
Язык: Английский
Процитировано
0Preliminary effects of risk-adapted PSA screening for prostate cancer after integrating PRS-specific and age-specific variation
Frontiers in Genetics, Год журнала: 2024, Номер 15
Опубликована: Авг. 1, 2024
Although the risk of prostate cancer (PCa) varies across different ages and genetic risks, it's unclear about effects genetic-specific age-specific prostate-specific antigen (PSA) screening for PCa.
Язык: Английский
Процитировано
0The Evolving Landscape of Prostate Cancer Care
Опубликована: Янв. 1, 2024
Язык: Английский
Процитировано
0