title: Genome-wide association scans for idiopathic osteonecrosis of the femoral head in a Korean population.
abstract: Osteonecrosis of the femoral head (ONFH) is a multifactorial disease and is associated with genetic predisposition, and exposure to certain risk factors. In particular, idiopathic ONFH in twins and the clustering of cases in families have indicated that genetic factors are involved. However, the majority of cases of ONFH are sporadic and various studies have demonstrated that differences in the study design and/or the ethnic groups analyzed leads to different results. The present study performed one of the first genome‑wide association studies to identify genetic loci that may increase the risk of idiopathic ONFH. In total, 217 patients with idiopathic ONFH and 217 control samples, without ONFH, were genotyped using Axiom™ chips. Following quality control, 509,886 single‑nucleotide polymorphisms (SNPs) were included in the association analysis to identify genetic variants that may influence susceptibility to idiopathic ONFH. The lowest P‑value identified by the current study was for an association with rs220324 (P=3.57x10‑7), an SNP that is located near to the uromodulin‑like 1 gene region on chromosome 21q22.3, although none of the SNPs reached the traditional genome‑wide significance level of 5x10‑8. However, the DnaJ heat shock protein family (Hsp40) member C6 (DNAJC6) locus, a region between 65.37 and 65.67 Mb located on chromosome 1p31.3, harbored a cluster of SNPs that were associated with idiopathic ONFH at a significance level of P<1x10‑5. Four variants, rs10493374, rs12032616, rs17127529 and rs6679032, with marginal associations were located in and around the DNAJC6 locus and were in strong linkage disequilibrium with each other. In conclusion, the current study did not identify any SNPs that were associated with idiopathic ONFH at a genome‑wide significance level, however, the results suggest that future studies should investigate the effects of SNPs in the DNAJC6 gene on the idiopathic ONFH risk.
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Baek
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Kang-Il
authors.initials: KI
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Kyung-Sik
authors.initials: KS
authors.lastname: Yoon
authors.affiliation: Biomedical Research Institute, Kyungpook National University Hospital, Daegu 41940, Republic of Korea.
authors.forename: Tae-Ho
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
authors.forename: Shin-Yoon
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005271:Femur Head Necrosis / Q000235:genetics* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea
chemical_list: C494652:DNAJC6 protein, human; D050956:HSP40 Heat-Shock Proteins