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Quantitative Trait Locus on Chromosome 1q Influences Bone Loss in Young Mexican American Adults

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Abstract

Bone loss occurs as early as the third decade and its cumulative effect throughout adulthood may impact risk for osteoporosis in later life, however, the genes and environmental factors influencing early bone loss are largely unknown. We investigated the role of genes in the change in bone mineral density (BMD) in participants in the San Antonio Family Osteoporosis Study. BMD change in 327 Mexican Americans (ages 25–45 years) from 32 extended pedigrees was calculated from DXA measurements at baseline and follow-up (3.5 to 8.9 years later). Family-based likelihood methods were used to estimate heritability (h 2) and perform autosome-wide linkage analysis for BMD change of the proximal femur and forearm and to estimate heritability for BMD change of lumbar spine. BMD change was significantly heritable for total hip, ultradistal radius, and 33% radius (h 2 = 0.34, 0.34, and 0.27, respectively; p < 0.03 for all), modestly heritable for femoral neck (h 2 = 0.22; p = 0.06) and not heritable for spine BMD. Covariates associated with BMD change included age, sex, baseline BMD, menopause, body mass index, and interim BMI change, and accounted for 6% to 24% of phenotype variation. A significant quantitative trait locus (LOD = 3.6) for femoral neck BMD change was observed on chromosome 1q23. In conclusion, we observed that change in BMD in young adults is heritable and performed one of the first linkage studies for BMD change. Linkage to chromosome 1q23 suggests that this region may harbor one or more genes involved in regulating early BMD change of the femoral neck.

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Acknowledgments

We are deeply grateful to the participants in the San Antonio Family Osteoporosis Study. We would also like to acknowledge two anonymous reviewers for their thoughtful suggestions. This work was funded by Grants M01-RR-01346, P01-HL-45522, R01-AR-43351, and R37-MH-59490, awarded by the National Institutes of Health.

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Authors and Affiliations

  1. Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, 130 DeSoto Street, A300 Crabtree Hall, GSPH, Pittsburgh, PA, 15213, USA

    John R. Shaffer & Candace M. Kammerer

  2. University of Texas Health Science Center, San Antonio, TX, USA

    Jan M. Bruder & Richard L. Bauer

  3. Southwest Foundation for Biomedical Research, San Antonio, TX, USA

    Shelley A. Cole, Thomas D. Dyer, Laura Almasy, Jean W. MacCluer & John Blangero

  4. Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA

    Braxton D. Mitchell

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  1. John R. Shaffer
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Correspondence to John R. Shaffer.

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Shaffer, J.R., Kammerer, C.M., Bruder, J.M. et al. Quantitative Trait Locus on Chromosome 1q Influences Bone Loss in Young Mexican American Adults. Calcif Tissue Int 84, 75–84 (2009). https://doi.org/10.1007/s00223-008-9197-3

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