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Comparative analysis of the Mexico City Prospective Study and the UK Biobank identifies ancestry-specific effects on clonal hematopoiesis

The impact of genetic ancestry on the development of clonal hematopoiesis (CH) remains largely unexplored. Here, we compared CH in 136,401 participants from the Mexico City Prospective Study (MCPS) to 416,118 individuals from the UK Biobank (UKB) and observed CH to be significantly less common in MCPS compared to UKB (adjusted odds ratio = 0.59, 95% confidence interval (CI) = [0.57, 0.61], P = 7.31 × 10−185). Among MCPS participants, CH frequency was positively correlated with the percentage of European ancestry (adjusted beta = 0.84, 95% CI = [0.66, 1.03], P = 7.35 × 10−19). Genome-wide and exome-wide association analyses in MCPS identified ancestry-specific variants in the TCL1B locus with opposing effects on DNMT3A-CH versus non-DNMT3A-CH. Meta-analysis of MCPS and UKB identified five novel loci associated with CH, including polymorphisms at PARP11/CCND2, MEIS1 and MYCN. Our CH study, the largest in a non-European population to date, demonstrates the power of cross-ancestry comparisons to derive novel insights into CH pathogenesis.

Feasibility of meeting future battery demand via domestic cell production in Europe

Batteries are critical to mitigate global warming, with battery electric vehicles as the backbone of low-carbon transport and the main driver of advances and demand for battery technology. However, the future demand and production of batteries remain uncertain, while the ambition to strengthen national capabilities and self-sufficiency is gaining momentum. In this study, leveraging probabilistic modelling, we assessed Europe’s capability to meet its future demand for high-energy batteries via domestic cell production. We found that demand in Europe is likely to exceed 1.0 TWh yr−1 by 2030 and thereby outpace domestic production, with production required to grow at highly ambitious growth rates of 31–68% yr−1. European production is very likely to cover at least 50–60% of the domestic demand by 2030, while 90% self-sufficiency seems feasible but far from certain. Thus, domestic production shortfalls are more likely than not. To support Europe’s battery prospects, stakeholders must accelerate the materialization of production capacities and reckon with demand growth post-2030, with reliable industrial policies supporting Europe’s competitiveness.

Assessment of polygenic risk score performance in East Asian populations for ten common diseases

Polygenic risk score (PRS) uses genetic variants to assess disease susceptibility. While PRS performance is well-studied in Europeans, its accuracy in East Asians is less explored. This study evaluated PRSs for ten diseases in the Health Examinees (HEXA) cohort (n = 55,870) in Korea. Single-population PRSs were constructed using PRS-CS, LDpred2, and Lassosum based on East Asian GWAS summary statistics (sample sizes: 51,442–341,204), while cross-population PRSs were developed using PRS-CSx and CT-SLEB by integrating European and East Asian GWAS data. PRS-CS consistently outperformed other single-population methods across key metrics, including the likelihood ratio test (LRT), odds ratio per standard deviation (perSD OR), net reclassification improvement (NRI), and area under the curve (AUC). Cross-population PRSs further improved predictive performance, with average increases of 1.08-fold (LRT), 1.07-fold (perSD OR), and 1.15-fold (NRI) across seven diseases with statistical significance, and a 1.01-fold improvement in AUC. Differences in R² between single- and cross-population PRSs were statistically significant for five diseases, showing an average increase of 1.13%. Cross-population PRSs achieved 87.8% of the predictive performance observed in European PRSs. These findings highlight the benefits of integrating European GWAS data while underscoring the need for larger East Asian datasets to improve prediction accuracy.

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