Polygenic risk scores (PRS) have attenuated cross-population predictive performance. As existing genomewide association studies (GWAS) were predominantly conducted in individuals of European descent, the limited transferability of PRS reduces its clinical value in non-European populations and may exacerbate healthcare disparities. Recent efforts to level ancestry imbalance in genomic research have expanded the scale of non-European GWAS, although they remain under-powered. Here we present a novel PRS construction method, PRS-CSx, which improves cross-population polygenic prediction by integrating GWAS summary statistics from multiple populations. PRS-CSx couples genetic effects across populations via a shared continuous shrinkage prior, enabling more accurate effect size estimation by sharing information between summary statistics and leveraging linkage disequilibrium (LD) diversity across discovery samples, while inheriting computational efficiency and robustness from PRS-CS. We show that PRS-CSx outperforms alternative methods across traits with a wide range of genetic architectures and cross-population genetic correlations in simulations, and substantially improves the prediction of quantitative traits and schizophrenia risk in non-European populations.

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Aims: Mild cognitive impairment (MCI) usually represents a transitional phase between normal cognitive function and dementia, but not all people with MCI develop dementia because MCI is a clinically and etiologically heterogeneous grouping. The aim of this study was to compare progression rates to Alzheimer’s disease (AD) among various MCI subtypes which show minimal white matter ischemia. Methods: Our study cohort consisted of 504 patients aged 55 years or older who had a diagnosis of MCI at their baseline visit, and had at least 1 follow-up contact after baseline. Results: Subjects with multiple-domain MCI with amnesia (mdMCI+a) were found to be significantly more likely to progress to AD in comparison to patients with nonamnesic MCI. There was no difference in the progression rate to AD between amnesic MCI and mdMCI+a during the follow-up period. The results of the multivariable Cox proportional hazards model analysis showed the same pattern of results as described above. Conclusion: Subjects with mdMCI+a had a statistically significant association with progression to AD. Especially, in cases of degenerative etiologies, impairment of the memory domain is more important than impairment of multiple domains in predicting the progression to dementia.