Dear Dr. Pajukanta and Co-authors,
I am reaching out regarding your recent publication, which raises several critical concerns that may significantly impact the interpretation and validity of its findings. The sample size in the KOBS cohort (n=8) is notably small, limiting the robustness of conclusions drawn, even with replication in the RYSA cohort. Additionally, statistical analyses, including iHS and EHH for selection signals, rely on allele frequency ranges with limited statistical power, making the robustness of these findings questionable. The exclusive focus on Finnish populations also restricts the study’s applicability to broader human populations. Moreover, claims linking rs10494217 to thermogenesis and cold adaptation rely heavily on murine models and lack experimental validation in human systems, which is essential to substantiate the proposed mechanisms.
Furthermore, transparency and reproducibility are significant issues. The study relies on proprietary tools and cohort-specific data, such as CELLECT and SAT bulk RNA-seq, which are not readily accessible for independent verification. Ambiguities in statistical adjustments, such as Bonferroni corrections and permutation validations, warrant clarification to ensure the integrity of the results. Additionally, some references, such as Fumagalli et al. (2015), may not directly support the claims made, raising concerns about the appropriateness of citations. I strongly recommend further validation through additional experiments, clarification of statistical methods, and consideration of issuing an erratum to address these issues transparently. Ensuring the reproducibility and rigor of this work is critical to maintaining its credibility within the scientific community.