Genetic variants affecting bone mineral density and bone mineral content at multiple skeletal sites in Hispanic children,Bone

当前位置： X-MOL 学术 › Bone › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Genetic variants affecting bone mineral density and bone mineral content at multiple skeletal sites in Hispanic children
Bone ( IF 3.5 ) Pub Date : 2020-03-01 , DOI: 10.1016/j.bone.2019.115175
Ruixue Hou ₁ , Shelley A Cole ₂ , Mariaelisa Graff ₃ , Karin Haack ₂ , Sandra Laston ₄ , Anthony G Comuzzie ₅ , Nitesh R Mehta ₆ , Kathleen Ryan ₇ , Diana L Cousminer ₈ , Babette S Zemel ₉ , Struan F A Grant ₁₀ , Braxton D Mitchell ₇ , Roman J Shypailo ₆ , Margaret L Gourlay ₁₁ , Kari E North ₃ , Nancy F Butte ₆ , V Saroja Voruganti ₁

Affiliation

Department of Nutrition and Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, USA.
Population Health Program, Texas Biomedical Research Institute, San Antonio, TX, USA.
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
South Texas Diabetes and Obesity Institute and Department of Human Genetics, University of Texas the Rio Grande Valley, Brownsville, TX, USA.
The Obesity Society, Silver Spring, MD, USA.
Department of Pediatrics and USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA.
Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.; Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD, USA.
Division of Human Genetics, Center for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, USA; Department of Genetics, University of Pennsylvania, USA.
Division of GI, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, University of Pennsylvania, Philadelphia, USA.
Division of Human Genetics, Center for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, USA; Department of Pediatrics, University of Pennsylvania, Philadelphia, USA; Department of Genetics, University of Pennsylvania, USA; Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Department of Family Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

CONTEXT Osteoporosis is a major public health burden with significant economic costs. However, the correlates of bone health in Hispanic children are understudied. OBJECTIVE We aimed to identify genetic variants associated with bone mineral density (BMD) and bone mineral content (BMC) at multiple skeletal sites in Hispanic children. METHODS We conducted a cross-sectional genome-wide linkage analysis, genome-wide and exome-wide association analysis of BMD and BMC. The Viva La Familia Study is a family-based cohort with a total of 1030 Hispanic children (4-19 years old at baseline) conducted in Houston, TX. BMD and BMC were measured by Dual-energy X-ray absorptiometry. RESULTS Significant heritability were observed for BMC and BMD at multiple skeletal sites ranging between 44 and 68% (P < 2.8 × 10-9). Significant evidence for linkage was found for BMD of pelvis and left leg on chromosome 7p14, lumbar spine on 20q13 and left rib on 6p21, and BMC of pelvis on chromosome 20q12 and total body on 14q22-23 (logarithm of odds score > 3). We found genome-wide significant association between BMC of right arm and rs762920 at PVALB (P = 4.6 × 10-8), and between pelvis BMD and rs7000615 at PTK2B (P = 7.4 × 10-8). Exome-wide association analysis revealed novel association of variants at MEGF10 and ABRAXAS2 with left arm and lumber spine BMC, respectively (P < 9 × 10-7). CONCLUSIONS We identified novel loci associated with BMC and BMD in Hispanic children, with strongest evidence for PTK2B. The findings provide better understanding of bone genetics and shed light on biological mechanisms underlying BMD and BMC variation.

中文翻译：

影响西班牙裔儿童多个骨骼部位骨矿物质密度和骨矿物质含量的遗传变异

背景骨质疏松症是一个重大的公共卫生负担，造成巨大的经济损失。然而，西班牙裔儿童骨骼健康的相关性尚未得到充分研究。目的我们的目的是确定西班牙裔儿童多个骨骼部位与骨矿物质密度 (BMD) 和骨矿物质含量 (BMC) 相关的遗传变异。方法我们对 BMD 和 BMC 进行了横断面全基因组连锁分析、全基因组和外显子组关联分析。Viva La Familia 研究是一项以家庭为基础的队列研究，共有 1030 名西班牙裔儿童（基线年龄为 4-19 岁），在德克萨斯州休斯顿进行。BMD和BMC通过双能X射线吸收法测量。结果在多个骨骼部位观察到 BMC 和 BMD 具有显着的遗传力，范围在 44% 至 68% 之间（P < 2.8 × 10-9）。在染色体 7p14 上发现了骨盆和左腿的 BMD、在 20q13 上的腰椎和在 6p21 上的左肋骨、以及在染色体 20q12 上的骨盆 BMC 和在 14q22-23 上的全身的 BMC（比值对数 > 3），发现了显着的关联证据。我们发现右臂 BMC 和 PVALB 的 rs762920 之间存在全基因组显着关联（P = 4.6 × 10-8），骨盆 BMD 和 PTK2B 的 rs7000615 之间存在全基因组显着关联（P = 7.4 × 10-8）。全外显子组关联分析揭示了 MEGF10 和 ABRAXAS2 变异分别与左臂和腰椎 BMC 的新关联 (P < 9 × 10-7)。结论我们在西班牙裔儿童中发现了与 BMC 和 BMD 相关的新位点，其中有关于 PTK2B 的最有力证据。这些发现有助于更好地理解骨遗传学，并揭示 BMD 和 BMC 变异的生物学机制。

更新日期：2020-03-01

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11