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

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.

骨大小（BS）是骨质疏松性骨折的主要危险因素之一。骨大小的变异在很大程度上由基因决定，遗传度超过50%，但骨大小变异的具体基因在很大程度上仍然未知。为了在中国人群中识别骨大小的特定基因，进行了初步的全基因组关联扫描（GWAS）研究以及后续的验证研究。在初步的GWAS研究中，一组12个连续的单核苷酸多态性（SNP），跨越约25kb的区域，位于HMGN3基因（高迁移率族核小体结合结构域3）的上游，对脊柱骨大小获得了中等程度的关联信号，P值范围从6.2×10⁻⁵到1.8×10⁻⁶。在后续的验证研究中，在1728名无关的女性白种人中检测到12个SNP中的8个与骨大小有提示性的重复关联，白种人与中国人在种族遗传背景上有显著差异。HMGN3基因区域的SNP在中国人和白种人中都形成了紧密结合的单倍型模块。结果表明，包含HMGN3基因的基因组区域可能与中国人的脊柱骨大小有关。