Genome-wide association study identifies HMGN3 locus for spine bone size variation in Chinese - PubMed (original) (raw)

doi: 10.1007/s00439-011-1093-7. Epub 2011 Sep 25.

Hui Shen, Tie-Lin Yang, Yan Guo, Shan-Shan Dong, Xiang-Hong Xu, Fei-Yan Deng, Qing Tian, Yong-Jun Liu, Yao-Zhong Liu, Jian Li, Hong-Wen Deng

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Genome-wide association study identifies HMGN3 locus for spine bone size variation in Chinese

Shu-Feng Lei et al. Hum Genet. 2012 Mar.

Abstract

Bone size (BS) is one of the major risk factors for osteoporotic fractures. BS variation is genetically determined to a substantial degree with heritability over 50%, but specific genes underlying variation of BS are still largely unknown. To identify specific genes for BS in Chinese, initial genome-wide association scan (GWAS) study and follow-up replication study were performed. In initial GWAS study, a group of 12 contiguous single-nucleotide polymorphism (SNP)s, which span a region of ~25 kb and locate at the upstream of HMGN3 gene (high-mobility group nucleosomal binding domain 3), achieved moderate association signals for spine BS, with P values ranging from 6.2E-05 to 1.8E-06. In the follow-up replication study, eight of the 12 SNPs were detected suggestive replicate associations with BS in 1,728 unrelated female Caucasians, which have well-known differences from Chinese in ethnic genetic background. The SNPs in the region of HMGN3 gene formed a tightly combined haplotype block in both Chinese and Caucasians. The results suggest that the genomic region containing HMGN3 gene may be associated with spine BS in Chinese.

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Figures

Fig. 1

Fig. 1

Quantile–quantile (Q–Q) plot for BS in Chinese. From the Q–Q plot, the observed P values for BS match the expected P values under the null distributions over the range of (1 < −log10(P) < 4.5)

Fig. 2

Fig. 2

Distribution of P values across the genome in association analyses. The −log10 P values from 689,368 SNPs in 1,627 Chinese are plotted according to its physical position on successive chromosomes. “P = 7.3E–08” is the conservative genome-wide threshold of Bonferroni correction in this study

Fig. 3

Fig. 3

Haplotype block for 12 SNPs detected in HMGN3 gene locus in Chinese. The detected SNPs are located at the upstream of HMGN3 (~200 kb). The LD patterns for the 12 SNPs were analyzed and plotted using the Haploview program

References

    1. Ahlborg HG, Johnell O, Turner CH, Rannevik G, Karlsson MK. Bone loss and bone size after menopause. N Engl J Med. 2003;349:327–334. - PubMed
    1. Augat P, Reeb H, Claes LE. Prediction of fracture load at different skeletal sites by geometric properties of the cortical shell. J Bone Miner Res. 1996;11:1356–1363. - PubMed
    1. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21:263–265. - PubMed
    1. Deng HW, Deng XT, Conway T, Xu FH, Heaney R, Recker RR. Determination of bone size of hip, spine, and wrist in human pedigrees by genetic and lifestyle factors. J Clin Densitom. 2002a;5:45–56. - PubMed
    1. Deng HW, Shen H, Xu FH, Deng HY, Conway T, Zhang HT, Recker RR. Tests of linkage and/or association of genes for vitamin D receptor, osteocalcin, and parathyroid hormone with bone mineral density. J Bone Miner Res. 2002b;17:678–686. - PubMed

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