期刊
BONE
卷 132, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2019.115175
关键词
Bone; Genetic variants; Hispanic; Children; Osteoporosis
资金
- NIH [MH59490, DK080457]
- USDA/Agricultural Research Service [625-51000-053]
- National Institutes of Health [R01 DK092238, R01 HD58886]
- American Diabetes Association [1-17-PDF-077]
- Institute for Translational Medicine and Therapeutics (ITMAT) Transdisciplinary Program in Translational Medicine and Therapeutics
- Daniel B. Burke Endowed Chair for Diabetes Research
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 x 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 x 10(-8)), and between pelvis BMD and rs7000615 at PTK2B (P = 7.4 x 10(-8)). Exome-wide association analysis revealed novel association of variants at MEGFIO and ABRAXAS2 with left arm and lumber spine BMC, respectively (P < 9 x 10(-7)). Conclusions: We identified novel loci associated with BMC and BMD in Hispanic children, with strongest evidence for PTK2B. These findings provide better understanding of bone genetics and shed light on biological mechanisms underlying BMD and BMC variation.
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