Heritability and Genetics of Serum Dickkopf 1 Levels in African Ancestry Families

Verfasser / Beitragende:
[Allison Kuipers, Shibing Yu, Candace Kammerer, Cara Nestlerode, Clareann Bunker, Alan Patrick, Victor Wheeler, Yingze Zhang, Joseph Zmuda]
Ort, Verlag, Jahr:
2015
Enthalten in:
Calcified Tissue International, 96/2(2015-02-01), 155-159
Format:
Artikel (online)
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024 7 0 |a 10.1007/s00223-014-9948-2  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00223-014-9948-2 
245 0 0 |a Heritability and Genetics of Serum Dickkopf 1 Levels in African Ancestry Families  |h [Elektronische Daten]  |c [Allison Kuipers, Shibing Yu, Candace Kammerer, Cara Nestlerode, Clareann Bunker, Alan Patrick, Victor Wheeler, Yingze Zhang, Joseph Zmuda] 
520 3 |a 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. 
540 |a Springer Science+Business Media New York, 2014 
690 7 |a Dickkopf-1  |2 nationallicence 
690 7 |a Heritability  |2 nationallicence 
690 7 |a Single nucleotide polymorphism  |2 nationallicence 
690 7 |a Gene expression  |2 nationallicence 
690 7 |a African ancestry  |2 nationallicence 
700 1 |a Kuipers  |D Allison  |u Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto St, A543 Crabtree Hall, 15261, Pittsburgh, PA, USA  |4 aut 
700 1 |a Yu  |D Shibing  |u Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA  |4 aut 
700 1 |a Kammerer  |D Candace  |u Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA  |4 aut 
700 1 |a Nestlerode  |D Cara  |u Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA  |4 aut 
700 1 |a Bunker  |D Clareann  |u Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA  |4 aut 
700 1 |a Patrick  |D Alan  |u Tobago Health Studies Office, Scarborough, Tobago, Trinidad and Tobago  |4 aut 
700 1 |a Wheeler  |D Victor  |u Tobago Health Studies Office, Scarborough, Tobago, Trinidad and Tobago  |4 aut 
700 1 |a Zhang  |D Yingze  |u Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA  |4 aut 
700 1 |a Zmuda  |D Joseph  |u Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA  |4 aut 
773 0 |t Calcified Tissue International  |d Springer US; http://www.springer-ny.com  |g 96/2(2015-02-01), 155-159  |x 0171-967X  |q 96:2<155  |1 2015  |2 96  |o 223 
856 4 0 |u https://doi.org/10.1007/s00223-014-9948-2  |q text/html  |z Onlinezugriff via DOI 
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900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00223-014-9948-2  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Kuipers  |D Allison  |u Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto St, A543 Crabtree Hall, 15261, Pittsburgh, PA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Yu  |D Shibing  |u Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Kammerer  |D Candace  |u Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Nestlerode  |D Cara  |u Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Bunker  |D Clareann  |u Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Patrick  |D Alan  |u Tobago Health Studies Office, Scarborough, Tobago, Trinidad and Tobago  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wheeler  |D Victor  |u Tobago Health Studies Office, Scarborough, Tobago, Trinidad and Tobago  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zhang  |D Yingze  |u Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zmuda  |D Joseph  |u Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Calcified Tissue International  |d Springer US; http://www.springer-ny.com  |g 96/2(2015-02-01), 155-159  |x 0171-967X  |q 96:2<155  |1 2015  |2 96  |o 223