Genome-wide meta-analysis identified novel variant associated with hallux valgus in Caucasians
JournalJournal of Foot and Ankle Research
PublisherBioMed Central Ltd.
MetadataShow full item record
AbstractBackground: Hallux valgus, one of the most common structural foot deformities, is highly heritable. However, previous efforts to elucidate the genetic underpinnings of hallux valgus through a genome-wide association study (GWAS) conducted in 4409 Caucasians did not identify genome-wide significant associations with hallux valgus in both gender-specific and sex-combined GWAS meta-analyses. In this analysis, we add newly available data and more densely imputed genotypes to identify novel genetic variants associated with hallux valgus. Methods: A total of 5925 individuals of European Ancestry were categorized into two groups: 'hallux valgus present' (n = 2314) or 'no deformity' (n = 3611) as determined by trained examiners or using the Manchester grading scale. Genotyping was performed using commercially available arrays followed by imputation to the Haplotype Reference Consortium (HRC) reference panel version 1.1. We conducted both sex-specific and sex-combined association analyses using logistic regression and generalized estimating equations as appropriate in each cohort. Results were then combined in a fixed-effects inverse-variance meta-analyses. Functional Mapping and Annotation web-based platform (FUMA) was used for positional mapping, gene and gene-set analyses. Results: We identified a novel locus in the intronic region of CLCA2 on chromosome 1, rs55807512 (OR = 0.48, p = 2.96E-09), an expression quantitative trait locus for COL24A1, a member of the collagen gene family. Conclusion: In this report of the largest GWAS of hallux valgus to date, we identified a novel genome-wide significant locus for hallux valgus. Additional replication and functional follow-up will be needed to determine the functional role of this locus in hallux valgus biology. Copyright 2020 The Author(s).
SponsorsJoCo was supported in part by S043, S1734, & S3486 from the Centers for Disease Control and Prevention/Association of Schools of Public Health; 5-P60-AR30701 & 5-P60 AR49465-03 from the National Institute of Arthritis Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH) and Algynomics, Inc. Ms. Arbeeva and Drs. Golightly, Nelson, and Jordan were supported by NIAMS Multidisciplinary Clinical Research Grant 5-P60 AR062760 and CDC 1U01DP006266. The conclusions are attributed to the authors and cannot be attributed to the CDC. The GOGO study was supported by GlaxoSmithKline. FHS was supported by R01-AR060492. The Osteoarthritis Initiative is a public-private partnership funded by the NIH (NIAMS contracts N01-AR-2-2258, N01-AR-2-2259, N01-AR-2-2260, N01-AR-2-2261, and N01-AR-2-2262). Genotyping in OAI was supported by the NIH (NIAMS RC2 AR058950). Additional support was provided by NIH grant P30-DK-072488, T32-AG-00262, and T32-AG-023480.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85081276141&doi=10.1186%2fs13047-020-0379-1&partnerID=40&md5=21da13e4a34a08b85bf03c720a966bc1; http://hdl.handle.net/10713/12309