{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:04:22Z","timestamp":1792789462064,"version":"4.5.0"},"reference-count":49,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"The Natural Science Foundation of China","doi-asserted-by":"crossref","award":["No. 82372497"],"award-info":[{"award-number":["No. 82372497"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Jiangsu Provincial Medical Innovation Center of Orthopedic Surgery","award":["CXZX202214"],"award-info":[{"award-number":["CXZX202214"]}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"crossref","award":["BK20240242"],"award-info":[{"award-number":["BK20240242"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Genetic factors have been increasingly recognized as important contributors to the development and progression of adolescent idiopathic scoliosis (AIS). However, the genetic basis underlying AIS curve severity remains largely unclear. The objective of this study is to identify novel genetic variants associated with curve severity in AIS through a genome-wide association study (GWAS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In the discovery stage, 620 female AIS patients were enrolled, including 323 with severe curves (&gt; 40\u00b0) and 297 with mild curves (&lt; 30\u00b0). Top single nucleotide polymorphisms (SNPs) from each locus were selected for replication in an independent cohort of 634 severe and 546 mild cases. Associations between gene expression and Cobb angle were evaluated using Spearman correlation, while correlations with myofiber\u2013related genes were analyzed using Pearson correlation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifteen novel SNPs showed potential association with AIS curve severity in the discovery stage (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a01\u00a0\u00d7\u00a010\n                      <jats:sup>\u22124<\/jats:sup>\n                      ). Six lead SNPs were selected for replication, including rs2061846 (\n                      <jats:italic>GAK<\/jats:italic>\n                      ), rs12200301 (\n                      <jats:italic>DST<\/jats:italic>\n                      ), rs10820637 (\n                      <jats:italic>SMC2\/NIPSNAP3A<\/jats:italic>\n                      ), rs7330031 (\n                      <jats:italic>KLF12<\/jats:italic>\n                      ), rs2469472 (\n                      <jats:italic>ST8SIA5-DT<\/jats:italic>\n                      ), and rs738650 (\n                      <jats:italic>SEZ6L<\/jats:italic>\n                      ). Among these, rs2061846 and rs7330031 were successfully replicated. For rs2061846 in\n                      <jats:italic>GAK<\/jats:italic>\n                      , the frequency of the G allele was significantly higher in the severe group (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.001; OR = 1.32). For rs7330031 in\n                      <jats:italic>KLF12<\/jats:italic>\n                      , the C allele was significantly more frequent in the severe group than in the mild group (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.001; OR = 1.46). Moreover,\n                      <jats:italic>KLF12<\/jats:italic>\n                      mRNA expression in the paraspinal muscle of AIS patients was negatively correlated with Cobb angle and associated with muscle fiber\u2013specific gene expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study identified\n                      <jats:italic>GAK<\/jats:italic>\n                      and\n                      <jats:italic>KLF12<\/jats:italic>\n                      as novel susceptibility genes associated with AIS curve severity, providing new insights into the genetic basis of curve progression. These findings may contribute to improved risk stratification and personalized management in AIS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.20638","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T08:40:20Z","timestamp":1768812020000},"page":"e20638","source":"Crossref","is-referenced-by-count":2,"title":["Genome-wide association study identifies\n                    <i>GAK<\/i>\n                    and\n                    <i>KLF12<\/i>\n                    associated with curve severity of adolescent idiopathic scoliosis"],"prefix":"10.7717","volume":"14","author":[{"given":"Zhicheng","family":"Dai","sequence":"first","affiliation":[{"name":"Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, China"},{"name":"Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital 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