A longitudinal genome-wide association study of bone mineral density mean and variability in the UK Biobank
A longitudinal genome-wide association study of bone mineral density mean and variability in the UK Biobank
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DOI：
10.1007/s00198-023-06852-1
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发表时间：
2023-07
影响因子：
4
通讯作者：
D. He;Huan Liu;Wenming Wei;Yijing Zhao;Q. Cai;S. Shi;Xiaoge Chu;X. Qin;Na Zhang;P. Xu;Feng Zhang
中科院分区：
文献类型：
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作者：
D. He;Huan Liu;Wenming Wei;Yijing Zhao;Q. Cai;S. Shi;Xiaoge Chu;X. Qin;Na Zhang;P. Xu;Feng Zhang
骨密度（BMD）是骨质疏松症和骨折的重要预测指标。我们进行了全基因组轨迹分析的BMD和分析的BMD changes.PurposeThis研究的目的是确定的遗传结构和潜在的生物标志物的BMD.MethodsOur分析包括141，261白色参与者从英国生物银行与脚跟BMD表型数据。我们使用全基因组轨迹分析工具TrajGWAS进行BMD的全基因组关联研究（GWAS）。然后，我们验证了我们的研究结果在以前报道的BMD遗传协会，并进行了复制分析，在亚洲参与者。结果共筛选出52个与BMD轨迹均值相关的基因，其中WNT 16（P= 1.31 × 10−126）、FAM 3C（P= 4.18 × 10−108）和CPED 1（P= 8.48 × 10 −106）为前3位显著基因。此外，还确定了114个与BMD受试者内变异相关的基因，如AC 092079.1（P= 2.72 × 10−13）和RGS 7（P= 4.72 × 10−10）。这些候选基因的关联在之前的GWAS中得到了证实，并在亚洲参与者中成功复制。BMD变化的GSEA结果确定了与骨骼发育相关的多个GO术语，如骨骼系统发育（P调整= 2.45 × 10−3）和骨化调节（P调整= 2.45 × 10−3）。KEGG富集分析表明，这些基因主要富集在WNT SIGNALING PATHWAY.ConclusionsOur研究结果表明，CPED 1-WNT 16-FAM 3基因座在BMD平均轨迹中起着重要作用，并确定了几个新的候选基因，有助于BMD受试者内变异性，促进对BMD遗传结构的理解。
Bone mineral density (BMD) is an essential predictor of osteoporosis and fracture. We conducted a genome-wide trajectory analysis of BMD and analyzed the BMD change.PurposeThis study aimed to identify the genetic architecture and potential biomarkers of BMD.MethodsOur analysis included 141,261 white participants from the UK Biobank with heel BMD phenotype data. We used a genome-wide trajectory analysis tool, TrajGWAS, to conduct a genome-wide association study (GWAS) of BMD. Then, we validated our findings in previously reported BMD genetic associations and performed replication analysis in the Asian participants. Finally, gene-set enrichment analysis (GSEA) of the identified candidate genes was conducted using the FUMA platform.ResultsA total of 52 genes associated with BMD trajectory mean were identified, of which the top three significant genes wereWNT16(P= 1.31 × 10−126),FAM3C(P= 4.18 × 10−108), andCPED1(P= 8.48 × 10−106). In addition, 114 genes associated with BMD within-subject variability were also identified, such asAC092079.1(P= 2.72 × 10−13) andRGS7(P= 4.72 × 10−10). The associations for these candidate genes were confirmed in the previous GWASs and replicated successfully in the Asian participants. GSEA results of BMD change identified multiple GO terms related to skeletal development, such as SKELETAL SYSTEM DEVELOPMENT (Padjusted= 2.45 × 10−3) and REGULATION OF OSSIFICATION (Padjusted= 2.45 × 10−3). KEGG enrichment analysis showed that these genes were mainly enriched in WNT SIGNALING PATHWAY.ConclusionsOur findings indicated that theCPED1-WNT16-FAM3Clocus plays a significant role in BMD mean trajectories and identified several novel candidate genes contributing to BMD within-subject variability, facilitating the understanding of the genetic architecture of BMD.