title: Admixture mapping of serum vitamin D and parathyroid hormone concentrations in the African American-Diabetes Heart Study.
abstract: Vitamin D and intact parathyroid hormone (iPTH) concentrations differ between individuals of African and European descent and may play a role in observed racial differences in bone mineral density (BMD). These findings suggest that mapping by admixture linkage disequilibrium (MALD) may be informative for identifying genetic variants contributing to these ethnic disparities. Admixture mapping was performed for serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, vitamin D-binding protein (VDBP), bioavailable vitamin D, and iPTH concentrations and computed tomography measured thoracic and lumbar vertebral volumetric BMD in 552 unrelated African Americans with type 2 diabetes from the African American-Diabetes Heart Study. Genotyping was performed using a custom Illumina ancestry informative marker (AIM) panel. For each AIM, the probability of inheriting 0, 1, or 2 copies of a European-derived allele was determined. Non-parametric linkage analysis was performed by testing for association between each AIM using these probabilities among phenotypes, accounting for global ancestry, age, and gender. Fine-mapping of MALD peaks was facilitated by genome-wide association study (GWAS) data. VDBP levels were significantly linked in proximity to the protein coding locus (rs7689609, LOD=11.05). Two loci exhibited significant linkage signals for 1,25-dihydroxyvitamin D on 13q21.2 (rs1622710, LOD=3.20) and 12q13.2 (rs11171526, LOD=3.10). iPTH was significantly linked on 9q31.3 (rs7854368, LOD=3.14). Fine-mapping with GWAS data revealed significant known (rs7041 with VDBP, P=1.38×10(-82)) and novel (rs12741813 and rs10863774 with VDBP, P<6.43×10(-5)) loci with plausible biological roles. Admixture mapping in combination with fine-mapping has focused efforts to identify loci contributing to ethnic differences in vitamin D-related traits.
authors.affiliation: Department of Biochemistry, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA; Center for Diabetes Research, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA; Center for Public Health Genomics, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA. Electronic address: nallred@wakehealth.edu.
authors.forename: Nicholette D
authors.initials: ND
authors.lastname: Palmer
authors.affiliation: Center for Public Health Genomics, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA; Department of Biostatistical Sciences, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA. Electronic address: jdivers@wakehealth.edu.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Divers
authors.affiliation: Center for Public Health Genomics, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA; Department of Biostatistical Sciences, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA. Electronic address: llu@wakehealth.edu.
authors.forename: Lingyi
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Pathology, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA. Electronic address: register@wakehealth.edu.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Register
authors.affiliation: Department of Radiology, Vanderbilt University School of Medicine, 2525 West End Ave, Suite 300-B, Nashville, TN 37203, USA. Electronic address: j.jeffrey.carr@vanderbilt.edu.
authors.forename: J Jeffrey
authors.initials: JJ
authors.lastname: Carr
authors.affiliation: Department of Biochemistry, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA. Electronic address: panderso@wakehealth.edu.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Hicks
authors.affiliation: Department of Biochemistry, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA. Electronic address: suscsmit@wakehealth.edu.
authors.forename: S Carrie
authors.initials: SC
authors.lastname: Smith
authors.affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA. Electronic address: jixu@wakehealth.edu.
authors.forename: Jianzhao
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL 35294, USA. Electronic address: sejudd@uab.edu.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Judd
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL 35294, USA. Electronic address: irvinr@uab.edu.
authors.forename: Marguerite R
authors.initials: MR
authors.lastname: Irvin
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL 35294, USA; Department of Medicine, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL, 35294, USA. Electronic address: ogutierr@uab.edu.
authors.forename: Orlando M
authors.initials: OM
authors.lastname: Gutierrez
authors.affiliation: Department of Biochemistry, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA; Center for Diabetes Research, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA. Electronic address: dbowden@wakehealth.edu.
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.affiliation: Division of Public Health Sciences, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA. Electronic address: lwgnkcht@wakehealth.edu.
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Wagenknecht
authors.affiliation: Center for Public Health Genomics, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA; Department of Biostatistical Sciences, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA. Electronic address: clangefe@wakehealth.edu.
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.affiliation: Center for Diabetes Research, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA; Center for Public Health Genomics, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA; Department of Internal Medicine-Section on Nephrology, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA. Electronic address: bfreedma@wakehealth.edu.
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
mesh_terms: D001741:Black or African American / Q000235:genetics*; D003710:Demography; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics*; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014807:Vitamin D / Q000097:blood*
chemical_list: D010281:Parathyroid Hormone; D014807:Vitamin D
keywords: Bone mineral density; Epidemiology; Human association studies; Intact parathyroid hormone; Vitamin D