The advent of next-generation sequencing technology is expected to accelerate the identification of novel genes, and this technology will likely supersede Sanger sequencing. Thus, genome-wide association studies (GWASs) are performed more routinely in an effort to identify disease-susceptibility genes for sporadic amyotrophic lateral sclerosis (ALS). Previously, a Japanese team conducted a large-scale GWAS with 1,305 Japanese ALS patients and discovered a new single nucleotide polymorphism (SNP) rs2275294 associated with susceptibility to sporadic ALS (sALS) in the ZNF512B gene on chromosome 20q13.33. Ju et al. recently performed a case-control study to examine the possible association of rs2275294 with the risk of sALS. Their results, however, indicated that the SNP in ZNF512B is not associated with sALS susceptibility in the Chinese population. A precise diagnosis of neurodegenerative diseases, especially ALS, is highly challenging. For GWASs and other clinical research studies that require a large sample size, if true ALS patients are not selected initially, then all subsequent research is futile. Here, I evaluate the factors that are likely responsible for the inconsistent results obtained by GWASs and propose the development of a new classification system and diagnostic criteria for ALS as the first step towards conducting better clinical studies on ALS. I have attempted to explain the reasons for the inconsistent association between rs2275294 and ALS progression by listing the gene-gene/gene-environment interactions, age of onset, sample size, odds ratio, and inappropriate ALS diagnosis criteria for stratifying this heterogeneous disease in this review.