title: A genome-wide association study of copy-number variation identifies putative loci associated with osteoarthritis in Koreans.
abstract: BACKGROUND
  OA is a complex disease caused by environmental and genetic risk factors. The purpose of this study is to identify candidate copy number variations (CNVs) associated with OA.
  
  
  METHODS
  We performed a genome-wide association study of CNV to identify potential loci that confer susceptibility to or protection from OA. CNV genotyping was conducted using NimbleGen HD2 3 × 720K comparative hybridization array and included samples from 371 OA patients and 467 healthy controls. The putative CNV regions identified were confirmed with a TaqMan assay.
  
  
  RESULTS
  We identified six genomic regions associated with OA encompassing CNV loci. None of six loci had previously been reported in genome-wide association studies with OA, although a genetic analysis suggested that they have functional effects. The protein product of a candidate risk gene for obesity, TNKS, targets Wnt inhibition, and this gene was significantly associated with hand and knee OA. Copy number deletion on TNKS was associated with a 1.37-fold decreased risk for OA. In addition, CA10, which shows a strong association with osteoporosis, was also significant in our study. Copy number deletion on this gene was associated with a 1.69-fold decreased risk for OA.
  
  
  CONCLUSIONS
  We identified several CNV loci that may contribute to OA susceptibility in Koreans. Further functional investigations of these genes are warranted to fully characterize their putative association.
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, 363-951, Chungchengbuk-Do, Republic of Korea. moon.sanghoon@daum.net.
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Moon
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, 363-951, Chungchengbuk-Do, Republic of Korea. bhumsuk@snu.ac.kr.|Department of Internal Medicine, Seoul National University Hospital, 110-744, Seoul, Republic of Korea. bhumsuk@snu.ac.kr.
authors.forename: Bhumsuk
authors.initials: B
authors.lastname: Keam
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, 363-951, Chungchengbuk-Do, Republic of Korea. myhwang85@gmail.com.
authors.forename: Mi Yeong
authors.initials: MY
authors.lastname: Hwang
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, 363-951, Chungchengbuk-Do, Republic of Korea. lyou7688@gmail.com.
authors.forename: Young
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, 363-951, Chungchengbuk-Do, Republic of Korea. sooyeon1002@gmail.com.|Department of Biostatistics, Soonchunhyang University, College of Medicine, 140-743, Seoul, Republic of Korea. sooyeon1002@gmail.com.
authors.forename: Suyeon
authors.initials: S
authors.lastname: Park
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, 363-951, Chungchengbuk-Do, Republic of Korea. ohjh83@gmail.com.
authors.forename: Ji Hee
authors.initials: JH
authors.lastname: Oh
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, 363-951, Chungchengbuk-Do, Republic of Korea. cocona35@hanmail.net.
authors.forename: Yeon-Jung
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, 363-951, Chungchengbuk-Do, Republic of Korea. hslee00@gmail.com.
authors.forename: Heun-Sik
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, 363-951, Chungchengbuk-Do, Republic of Korea. shnhkim@hanmail.net.
authors.forename: Nam Hee
authors.initials: NH
authors.lastname: Kim
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, 363-951, Chungchengbuk-Do, Republic of Korea. anwltlarkr@gmail.com.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Social and Preventive Medicine, Hallym University College of Medicine, 200-702, Chunchun, Republic of Korea. dhkims@hallym.ac.kr.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, 363-951, Chungchengbuk-Do, Republic of Korea. bokghee@korea.kr.
authors.forename: Bok-Ghee
authors.initials: BG
authors.lastname: Han
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, 363-951, Chungchengbuk-Do, Republic of Korea. kbj6181@cdc.go.kr.
authors.forename: Bong-Jo
authors.initials: BJ
authors.lastname: Kim
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, 363-951, Chungchengbuk-Do, Republic of Korea. jylee@cdc.go.kr.
authors.forename: Juyoung
authors.initials: J
authors.lastname: Lee
mesh_terms: D016022:Case-Control Studies; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010003:Osteoarthritis / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D010024:Osteoporosis / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D038501:Tankyrases / Q000235:genetics*
chemical_list: D009419:Nerve Tissue Proteins; D038501:Tankyrases; C512815:CA10 protein, human; C418109:TNKS protein, human