Department of Biomedical and Nutritional Sciences and Center for Population Health, University of Massachusetts Lowell, Lowell, MA 01854, USA.
JM-US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, USDA ARS, Nutrition and Genomics Laboratory, Boston, MA 02111, USA.
J Bone Miner Res. 2024 Jul 23;39(6):697-706. doi: 10.1093/jbmr/zjae047.
Osteoporosis (OP) and low bone mass can be debilitating and costly conditions if not acted on quickly. This disease is also difficult to diagnose as the symptoms develop unnoticed until fracture occurs. Therefore, gaining understanding of the genetic risk associated with these conditions could be beneficial for health-care professionals in early detection and prevention. The Boston Puerto Rican Osteoporosis (BPROS) study, an ancillary study to the Boston Puerto Rican Health Study (BPRHS), collected information regarding bone and bone health. All bone measurements were taken during regular BPROS visits using dual-energy X-ray absorptiometry. The OP was defined as T-score ≤ -2.5 (≥2.5 SDs below peak bone mass). Dietary variables were collected at the second wave of the BPRHS via a food frequency questionnaire. We conducted genome-wide associations with bone outcomes, including BMD and OP for 978 participants. We also examined the interactions with dietary quality on the relationships between genotype and bone outcomes. We further tested if candidate genetic variants described in previous GWAS on OP and BMD contribute to OP risk in this population. Four variants were associated with OP: rs114829316 (IQ motif containing J gene), rs76603051, rs12214684 (melanin-concentrating hormone receptor 2 gene), and rs77303493 (Ras and Rab interactor 2 gene), and 2 variants were associated with BMD of lumbar spine (rs11855618, cingulin-like 1 gene) and hip (rs73480593, NTRK2), reaching the genome-wide significance threshold of P ≤ 5E-08. In a gene-diet interaction analysis, we found that 1 SNP showed a significant interaction with the overall Dietary Approaches to Stop Hypertension (DASH) score, and 7 SNPs with sugar-sweetened beverages (SSBs), a major contributor to the DASH score. This study identifies new genetic markers related to OP and BMD in older Hispanic adults. Additionally, we uncovered unique genetic markers that interact with dietary quality, specifically SSBs, in relation to bone health. These findings may be useful to guide early detection and preventative care.
骨质疏松症(OP)和低骨量如果不及时治疗,可能会导致身体虚弱和花费高昂。这种疾病也很难诊断,因为症状在骨折发生之前是察觉不到的。因此,了解与这些情况相关的遗传风险对医疗保健专业人员进行早期检测和预防可能是有益的。波士顿波多黎各骨质疏松症(BPROS)研究是波士顿波多黎各健康研究(BPRHS)的一个辅助研究,收集了有关骨骼和骨骼健康的信息。所有骨骼测量都是在 BPROS 定期就诊时使用双能 X 射线吸收法进行的。骨质疏松症的定义为 T 评分≤-2.5(骨峰值以下≥2.5 个标准差)。通过 BPRHS 的第二波收集饮食变量,使用食物频率问卷。我们对 978 名参与者的骨骼结果(包括骨密度和骨质疏松症)进行了全基因组关联分析。我们还研究了饮食质量对基因型与骨骼结果之间关系的交互作用。我们进一步测试了以前关于骨质疏松症和骨密度的 GWAS 中描述的候选遗传变异是否会导致该人群的骨质疏松症风险。有四个变体与骨质疏松症相关:rs114829316(包含 IQ 基序的 J 基因)、rs76603051、rs12214684(黑色素浓缩激素受体 2 基因)和 rs77303493(Ras 和 Rab 相互作用 2 基因),有两个变体与腰椎(rs11855618,腱样蛋白 1 基因)和臀部(rs73480593,NTRK2)的骨密度相关,达到了全基因组意义阈值 P≤5E-08。在基因-饮食相互作用分析中,我们发现 1 个 SNP 与总体饮食方法停止高血压(DASH)评分有显著相互作用,7 个 SNP 与含糖饮料(SSB)有显著相互作用,SSB 是 DASH 评分的主要贡献者。这项研究确定了与老年西班牙裔成年人骨质疏松症和骨密度相关的新遗传标记。此外,我们还发现了与饮食质量(特别是 SSB)相互作用的独特遗传标记与骨骼健康有关。这些发现可能有助于指导早期检测和预防保健。