Novel Genetic Variants Associated with Lumbar Spondylosis in Koreans: A Genome-Wide Association Study

OBJECTIVE: The aim of this study was to identify the susceptibility genes responsible for lumbar spondylosis (LS) in Korean patients.METHODS: Data from 1427 subjects were made available for radiographic grading and genome wide association studies (GWAS) analysis. Lateral lumbar spine radiographs were obtained and the various degrees of degenerative change were semi-quantitatively scored. A pilot GWAS was performed using the AffymetrixGenome-Wide Human single-nucleotide polymorphisms (SNPs), 500K array. A total of 352228 SNPs were analyzed and the association between the SNPs and case-control status was analyzed by stepwise logistic regression analyses.RESULTS: The top 100 SNPs with a cutoff p-value of less than 3.7×10⁻⁴ were selected for joint space narrowing, while a cutoff p-value of 6.0×10⁻⁴ was applied to osteophytes and the Kellgren-Lawrence (K-L) osteoarthritis grade. The SNPs with the strongest effect on disc space narrowing, osteophytes, and K-L grade were serine incorporator 1 (rs155467, odds ratio [OR]=17.58, p=1.6×10⁻⁴), stromal interaction molecule 2 (STIM1, rs210781, OR=5.53, p=5×10⁻⁴), and transient receptor potential cation channel, subfamily C (rs11224760, OR=3.99, p=4.8×10⁻⁴), respectively. Leucine-rich repeat-containing G protein-coupled receptor 4 was significantly associated with both disc space narrowing and osteophytes (rs1979400, OR=2.01, p=1.1×10⁻⁴ for disc space narrowing, OR=1.79, p=3×10⁻⁴ for osteophytes), while zinc finger and BTB domain containing 7C was significantly and negatively associated with both osteophytes and a K-L grade >2 (rs12457004,OR=0.25, p=5.8×10⁻⁴ and OR=0.27, p=5.3×10⁻⁴, respectively).CONCLUSION: We identified SNPs that potentially contribute to the pathogenesis of LS. This is the first report of a GWAS in an Asian population.

Novel Genetic Variants Associated with Lumbar Spondylosis in Koreans: A Genome-Wide Association Study

OBJECTIVE: The aim of this study was to identify the susceptibility genes responsible for lumbar spondylosis (LS) in Korean patients. METHODS: Data from 1427 subjects were made available for radiographic grading and genome wide association studies (GWAS) analysis. Lateral lumbar spine radiographs were obtained and the various degrees of degenerative change were semi-quantitatively scored. A pilot GWAS was performed using the AffymetrixGenome-Wide Human single-nucleotide polymorphisms (SNPs), 500K array. A total of 352228 SNPs were analyzed and the association between the SNPs and case-control status was analyzed by stepwise logistic regression analyses. RESULTS: The top 100 SNPs with a cutoff p-value of less than 3.7×10⁻⁴ were selected for joint space narrowing, while a cutoff p-value of 6.0×10⁻⁴ was applied to osteophytes and the Kellgren-Lawrence (K-L) osteoarthritis grade. The SNPs with the strongest effect on disc space narrowing, osteophytes, and K-L grade were serine incorporator 1 (rs155467, odds ratio [OR]=17.58, p=1.6×10⁻⁴), stromal interaction molecule 2 (STIM1, rs210781, OR=5.53, p=5×10⁻⁴), and transient receptor potential cation channel, subfamily C (rs11224760, OR=3.99, p=4.8×10⁻⁴), respectively. Leucine-rich repeat-containing G protein-coupled receptor 4 was significantly associated with both disc space narrowing and osteophytes (rs1979400, OR=2.01, p=1.1×10⁻⁴ for disc space narrowing, OR=1.79, p=3×10⁻⁴ for osteophytes), while zinc finger and BTB domain containing 7C was significantly and negatively associated with both osteophytes and a K-L grade >2 (rs12457004,OR=0.25, p=5.8×10⁻⁴ and OR=0.27, p=5.3×10⁻⁴, respectively). CONCLUSION: We identified SNPs that potentially contribute to the pathogenesis of LS. This is the first report of a GWAS in an Asian population.

Genetic Risk Prediction for Normal-Karyotype Acute Myeloid Leukemia Using Whole-Exome Sequencing

Normal-karyotype acute myeloid leukemia (NK-AML) is a highly malignant and cytogenetically heterogeneous hematologic cancer. We searched for somatic mutations from 10 pairs of tumor and normal cells by using a highly efficient and reliable analysis workflow for whole-exome sequencing data and performed association tests between the NK-AML and somatic mutations. We identified 21 nonsynonymous single nucleotide variants (SNVs) located in a coding region of 18 genes. Among them, the SNVs of three leukemia-related genes (MUC4, CNTNAP2, and GNAS) reported in previous studies were replicated in this study. We conducted stepwise genetic risk score (GRS) models composed of the NK-AML susceptible variants and evaluated the prediction accuracy of each GRS model by computing the area under the receiver operating characteristic curve (AUC). The GRS model that was composed of five SNVs (rs75156964, rs56213454, rs6604516, rs10888338, and rs2443878) showed 100% prediction accuracy, and the combined effect of the three reported genes was validated in the current study (AUC, 0.98; 95% confidence interval, 0.92 to 1.00). Further study with large sample sizes is warranted to validate the combined effect of these somatic point mutations, and the discovery of novel markers may provide an opportunity to develop novel diagnostic and therapeutic targets for NK-AML.