caa a22 4500 60552162X CHVBK 20210128100741.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s00223-014-9948-2 doi (NATIONALLICENCE)springer-10.1007/s00223-014-9948-2 Heritability and Genetics of Serum Dickkopf 1 Levels in African Ancestry Families [Elektronische Daten] [Allison Kuipers, Shibing Yu, Candace Kammerer, Cara Nestlerode, Clareann Bunker, Alan Patrick, Victor Wheeler, Yingze Zhang, Joseph Zmuda] 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 1724.1pg/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. Springer Science+Business Media New York, 2014 Dickkopf-1 nationallicence Heritability nationallicence Single nucleotide polymorphism nationallicence Gene expression nationallicence African ancestry nationallicence Kuipers Allison Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto St, A543 Crabtree Hall, 15261, Pittsburgh, PA, USA aut Yu Shibing Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA aut Kammerer Candace Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA aut Nestlerode Cara Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA aut Bunker Clareann Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA aut Patrick Alan Tobago Health Studies Office, Scarborough, Tobago, Trinidad and Tobago aut Wheeler Victor Tobago Health Studies Office, Scarborough, Tobago, Trinidad and Tobago aut Zhang Yingze Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA aut Zmuda Joseph Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA aut Calcified Tissue International Springer US; http://www.springer-ny.com 96/2(2015-02-01), 155-159 0171-967X 96:2<155 2015 96 223 https://doi.org/10.1007/s00223-014-9948-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00223-014-9948-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kuipers Allison Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto St, A543 Crabtree Hall, 15261, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Yu Shibing Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Kammerer Candace Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Nestlerode Cara Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Bunker Clareann Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Patrick Alan Tobago Health Studies Office, Scarborough, Tobago, Trinidad and Tobago aut NATIONALLICENCE 700 1- Wheeler Victor Tobago Health Studies Office, Scarborough, Tobago, Trinidad and Tobago aut NATIONALLICENCE 700 1- Zhang Yingze Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Zmuda Joseph Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA aut NATIONALLICENCE 773 0- Calcified Tissue International Springer US; http://www.springer-ny.com 96/2(2015-02-01), 155-159 0171-967X 96:2<155 2015 96 223