title: Linkage and association analysis of circulating vitamin D and parathyroid hormone identifies novel loci in Alaska Native Yup'ik people.
abstract: BACKGROUND
  Vitamin D deficiency is a well-documented public health issue with both genetic and environmental determinants. Populations living at far northern latitudes are vulnerable to vitamin D deficiency and its health sequelae, although consumption of traditional native dietary pattern rich in fish and marine mammals may buffer the effects of reduced sunlight exposure. To date, few studies have investigated the genetics of vitamin D metabolism in circumpolar populations or considered genediet interactions with fish and n-3 fatty acid intake.
  
  
  METHODS
  We searched for genomic regions exhibiting linkage and association with circulating levels of vitamin D and parathyroid hormone (PTH) in 982 Yup'ik individuals from the Center for Alaska Native Health Research Study. We also investigated potential interactions between genetic variants and a biomarker of traditional dietary intake, the δ15N value.
  
  
  RESULTS
  We identified several novel regions linked with circulating vitamin D and PTH as well as replicated a previous linkage finding on 2p16.2 for vitamin D. Bioinformatic analysis revealed multiple candidate genes for both PTH and vitamin D, including CUBN, MGAT3, and NFKBIA. Targeted association analysis identified NEBL as a candidate gene for vitamin D and FNDC3B for PTH. We observed significant associations between a variant in MXD1 and vitamin D only when an interaction with the δ15N value was included. Finally, we integrated pathway level information to illustrate the biological validity of the proposed candidate genes.
  
  
  CONCLUSIONS
  We provide evidence of linkage between several biologically plausible genomic regions and vitamin D metabolism in a circumpolar population. Additionally, these findings suggest that a traditional dietary pattern may modulate genetic effects on circulating vitamin D.
authors: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL USA.
authors: Stella
authors: S
authors: Aslibekyan
authors: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL USA ; Department of Biology, King University, Bristol, TN USA.
authors: Laura K
authors: LK
authors: Vaughan
authors: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL USA.
authors: Howard W
authors: HW
authors: Wiener
authors: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL USA.
authors: Bertha A
authors: BA
authors: Hidalgo
authors: Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, FL USA.
authors: Dominick J
authors: DJ
authors: Lemas
authors: Center for Alaska Native Health Research, Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK USA.
authors: Diane M
authors: DM
authors: O'Brien
authors: Center for Alaska Native Health Research, Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK USA.
authors: Scarlett E
authors: SE
authors: Hopkins
authors: Departments of Molecular Biosciences and Nutrition, University of California at Davis, Davis, CA USA.
authors: Kimber L
authors: KL
authors: Stanhope
authors: Departments of Molecular Biosciences and Nutrition, University of California at Davis, Davis, CA USA.
authors: Peter J
authors: PJ
authors: Havel
authors: Department of Pharmaceutics, University of Washington, Seattle, WA USA.
authors: Kenneth E
authors: KE
authors: Thummel
authors: Center for Alaska Native Health Research, Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK USA.
authors: Bert B
authors: BB
authors: Boyer
authors: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL USA.
authors: Hemant K
authors: HK
authors: Tiwari
keywords: Alaska Native; Linkage; Parathyroid hormone; Vitamin D; n-3 fatty acids