Although the sample size of candidate gene association studies has increased over the years (Supplementary Figure 1A), genetic power calculation and corresponding sample size ascertainment should always be a top priority before conducting genetic studies. Additionally, only 18% and 10% of the 287 studies investigated subjects with African and Asian ancestries, respectively, compared with 69% for European ancestry (Supplementary Figure 1B). Studying different populations is necessary to understand the genetic causes of ND in various ethnic groups. Concurrently, given the importance of rare variants suggested by targeted sequencing study results, thorough and well-powered genomic evaluations at the lower end of the allelic spectrum are needed. Whole-exome and whole-genome sequencing studies with enough statistical rigor would enable a substantial update of the ND genetic susceptibility map in the near future.
