Abstract
The aim of the study was to determine the heritability of serum dickkopf-1 (DKK1) and its association with DKK1 polymorphisms in African ancestry subjects. Serum DKK1 was measured in 422 Afro–Caribbean men and women aged 18+ from 7 large, multi-generational families (mean family size: 60; 3,215 relative pairs). Twenty-four common single nucleotide polymorphisms (SNPs) were genotyped within an 80 kilobase-pair region encompassing the DKK1 gene. Heritability was estimated and SNPs were tested for association with serum DKK1 using variance components analysis. DKK1 mRNA expression was tested in peripheral blood of 16 individuals from each of the rs7069912 genotypes. Mean serum DKK1 was 1724.1 pg/mL and was significantly lower in women than men (P = 0.043). Residual genetic heritability of serum DKK1 was 0.4460 (P < 0.0001). Six SNPs reached nominal significance with DKK1, with rs7069912 being significant after adjustment for multiple comparisons. Two of these six SNPs represented independent association signals (rs7069912 and rs16928725), which accounted for 4.6 % of the phenotypic variation in DKK1. Additionally, carriers of the rs7069912 variant had significantly greater DKK1 expression than non-carriers (P = 0.036). Serum DKK1 levels are highly heritable in the African ancestry families. Two SNPs within the DKK1 region accounted for nearly 5 % of the variation in serum DKK1.
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Acknowledgments
This work was supported by the National Institutes of Health Grants R01-AR049747 and R03-AR050107 from the National Institute of Arthritis, Musculoskeletal and Skin Diseases and R01-AG033618 from the National Institute on Aging. Dr. Kuipers was funded by the National Heart, Lung and Blood Institute Grant T32-HL083825.
Conflict of interest
Allison L. Kuipers, Shibing Yu, Candace M. Kammerer, Cara S. Nestlerode, Clareann H. Bunker, Alan L. Patrick, Victor W. Wheeler, Yingze Zhang, and Joseph M. Zmuda declare that they have no conflicts of interest.
Human and Animal Rights and Informed Consent
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors. Informed consent was obtained from all individual participants included in the study.
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Kuipers, A.L., Yu, S., Kammerer, C.M. et al. Heritability and Genetics of Serum Dickkopf 1 Levels in African Ancestry Families. Calcif Tissue Int 96, 155–159 (2015). https://doi.org/10.1007/s00223-014-9948-2
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DOI: https://doi.org/10.1007/s00223-014-9948-2