Linkage and association analysis of circulating vitamin D and parathyroid hormone identifies novel loci in Alaska Native Yup'ik people.
BackgroundVitamin 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 fi...
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ftcdlib:oai:escholarship.org/ark:/13030/qt7140r957 2023-05-15T15:13:37+02:00 Linkage and association analysis of circulating vitamin D and parathyroid hormone identifies novel loci in Alaska Native Yup'ik people. Aslibekyan, Stella Vaughan, Laura K Wiener, Howard W Hidalgo, Bertha A Lemas, Dominick J O'Brien, Diane M Hopkins, Scarlett E Stanhope, Kimber L Havel, Peter J Thummel, Kenneth E Boyer, Bert B Tiwari, Hemant K 23 2016-01-01 application/pdf https://escholarship.org/uc/item/7140r957 unknown eScholarship, University of California qt7140r957 https://escholarship.org/uc/item/7140r957 public Genes & nutrition, vol 11, iss 1 Alaska Native Linkage Parathyroid hormone Vitamin D n-3 fatty acids Clinical Research American Indian or Alaska Native Complementary and Alternative Medicine Genetics Nutrition Arctic Human Genome Metabolic and Endocrine Nutrition & Dietetics article 2016 ftcdlib 2021-02-18T15:15:24Z BackgroundVitamin 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.MethodsWe 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.ResultsWe 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.ConclusionWe 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. Article in Journal/Newspaper Arctic Yup'ik Alaska University of California: eScholarship Arctic Indian |
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topic |
Alaska Native Linkage Parathyroid hormone Vitamin D n-3 fatty acids Clinical Research American Indian or Alaska Native Complementary and Alternative Medicine Genetics Nutrition Arctic Human Genome Metabolic and Endocrine Nutrition & Dietetics |
spellingShingle |
Alaska Native Linkage Parathyroid hormone Vitamin D n-3 fatty acids Clinical Research American Indian or Alaska Native Complementary and Alternative Medicine Genetics Nutrition Arctic Human Genome Metabolic and Endocrine Nutrition & Dietetics Aslibekyan, Stella Vaughan, Laura K Wiener, Howard W Hidalgo, Bertha A Lemas, Dominick J O'Brien, Diane M Hopkins, Scarlett E Stanhope, Kimber L Havel, Peter J Thummel, Kenneth E Boyer, Bert B Tiwari, Hemant K Linkage and association analysis of circulating vitamin D and parathyroid hormone identifies novel loci in Alaska Native Yup'ik people. |
topic_facet |
Alaska Native Linkage Parathyroid hormone Vitamin D n-3 fatty acids Clinical Research American Indian or Alaska Native Complementary and Alternative Medicine Genetics Nutrition Arctic Human Genome Metabolic and Endocrine Nutrition & Dietetics |
description |
BackgroundVitamin 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.MethodsWe 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.ResultsWe 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.ConclusionWe 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. |
format |
Article in Journal/Newspaper |
author |
Aslibekyan, Stella Vaughan, Laura K Wiener, Howard W Hidalgo, Bertha A Lemas, Dominick J O'Brien, Diane M Hopkins, Scarlett E Stanhope, Kimber L Havel, Peter J Thummel, Kenneth E Boyer, Bert B Tiwari, Hemant K |
author_facet |
Aslibekyan, Stella Vaughan, Laura K Wiener, Howard W Hidalgo, Bertha A Lemas, Dominick J O'Brien, Diane M Hopkins, Scarlett E Stanhope, Kimber L Havel, Peter J Thummel, Kenneth E Boyer, Bert B Tiwari, Hemant K |
author_sort |
Aslibekyan, Stella |
title |
Linkage and association analysis of circulating vitamin D and parathyroid hormone identifies novel loci in Alaska Native Yup'ik people. |
title_short |
Linkage and association analysis of circulating vitamin D and parathyroid hormone identifies novel loci in Alaska Native Yup'ik people. |
title_full |
Linkage and association analysis of circulating vitamin D and parathyroid hormone identifies novel loci in Alaska Native Yup'ik people. |
title_fullStr |
Linkage and association analysis of circulating vitamin D and parathyroid hormone identifies novel loci in Alaska Native Yup'ik people. |
title_full_unstemmed |
Linkage and association analysis of circulating vitamin D and parathyroid hormone identifies novel loci in Alaska Native Yup'ik people. |
title_sort |
linkage and association analysis of circulating vitamin d and parathyroid hormone identifies novel loci in alaska native yup'ik people. |
publisher |
eScholarship, University of California |
publishDate |
2016 |
url |
https://escholarship.org/uc/item/7140r957 |
op_coverage |
23 |
geographic |
Arctic Indian |
geographic_facet |
Arctic Indian |
genre |
Arctic Yup'ik Alaska |
genre_facet |
Arctic Yup'ik Alaska |
op_source |
Genes & nutrition, vol 11, iss 1 |
op_relation |
qt7140r957 https://escholarship.org/uc/item/7140r957 |
op_rights |
public |
_version_ |
1766344143882158080 |