A genome-wide association study identifies four susceptibility loci for keloid in the Japanese population

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Keloid is a dermal fibroproliferative growth that results from dysfunction of the wound healing processes. Through a multistage genome-wide association study using 824 individuals with keloid (cases) and 3,205 unaffected controls in the Japanese population, we identified significant associations of keloid with four SNP loci in three chromosomal regions: 1q41, 3q22.3–23 and 15q21.3. The most significant association with keloid was observed at rs873549 (combined P = 5.89 × 10−23, odds ratio (OR) = 1.77) on chromosome 1. Associations on chromosome 3 were observed at two separate linkage disequilibrium (LD) blocks: rs1511412 in the LD block including FOXL2 with P = 2.31 × 10−13 (OR = 1.87) and rs940187 in another LD block with P = 1.80 × 10−13 (OR = 1.98). Association of rs8032158 located in NEDD4 on chromosome 15 yielded P = 5.96 × 10−13 (OR = 1.51). Our findings provide new insights into the pathophysiology of keloid formation.

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Figure 1: Results from a two-stage genome-wide association study.
Figure 2: Case-control association results and linkage disequilibrium maps of the candidate regions.


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We express our heartfelt gratitude to all the subjects who participated in this study and the members of the Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan for supporting our study. We would like to thank S.-K. Low for her assistance in the statistical analysis. We also thank the technical staff of the Laboratory for Genotyping Development in RIKEN. We would like to express our gratefulness to T. Tamamoto and K. Matsuda for their outstanding technical assistance. This work was conducted as a part of the BioBank Japan Project that was supported by the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government.

Author information

Y.N. conceived the study. Y.N., H.Z., M.N., S.C. and M.K. designed the study. M.N., N.H. and M.K. performed the genotyping. M.N., A.T., N.K., T.K. and T.T. performed the data analyses. Y.N., H.Z. and M.K. managed DNA samples belonging to BioBank Japan. M.N. summarized the results. M.N., H.Z., M.K. and Y.N. wrote the manuscript. Y.N. obtained funding for the study.

Correspondence to Yusuke Nakamura.

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