Your cohort consists exclusively of 32 White, non-Hispanic patients. While this homogeneity can reduce genetic and environmental variability, it also raises questions about whether the observed associations, particularly those involving genetic factors such as the MAPT H1/H2 haplotypes and TMEM106B genotypes, are applicable to other ancestral or ethnic groups.
Given that the frequencies of these genetic variants, as well as the prevalence and expression of 4R-tauopathies, can differ across populations, the lack of diversity may limit the extrapolation of your results. For example, the reported lower H1 haplotype frequency in PAOS-PSP compared to typical Richardson’s syndrome could be influenced by the specific genetic background of your cohort.
Could you please comment on:
Whether you have plans to replicate these findings in more diverse cohorts?
How you interpret the potential impact of population stratification on your genetic and pathological associations?
Whether the clinical and imaging biomarkers you identified (e.g., phonetic vs. prosodic subtypes, corticostriatal vs. PNL network involvement) have been studied in non-White populations?