Genetic determinants of glycated hemoglobin levels in the Greenlandic Inuit population
We previously showed that a common genetic variant leads to a remarkably increased risk of type 2 diabetes (T2D) in the small and historically isolated Greenlandic population. Motivated by this, we aimed at discovering novel genetic determinants for glycated hemoglobin (HbA 1C) and at estimating the...
Published in: | European Journal of Human Genetics |
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Format: | Article in Journal/Newspaper |
Language: | English |
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2018
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Online Access: | https://portal.findresearcher.sdu.dk/da/publications/3c4858f2-8fcd-4fcc-907b-95ed153add3e https://doi.org/10.1038/s41431-018-0109-3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974304/pdf/41431_2018_Article_109.pdf |
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ftsydanskunivpub:oai:sdu.dk:publications/3c4858f2-8fcd-4fcc-907b-95ed153add3e 2024-06-23T07:53:25+00:00 Genetic determinants of glycated hemoglobin levels in the Greenlandic Inuit population Appel, Emil V.R. Moltke, Ida Jørgensen, Marit E. Bjerregaard, Peter Linneberg, Allan Pedersen, Oluf Albrechtsen, Anders Hansen, Torben Grarup, Niels 2018-06 https://portal.findresearcher.sdu.dk/da/publications/3c4858f2-8fcd-4fcc-907b-95ed153add3e https://doi.org/10.1038/s41431-018-0109-3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974304/pdf/41431_2018_Article_109.pdf eng eng https://portal.findresearcher.sdu.dk/da/publications/3c4858f2-8fcd-4fcc-907b-95ed153add3e info:eu-repo/semantics/openAccess Appel , E V R , Moltke , I , Jørgensen , M E , Bjerregaard , P , Linneberg , A , Pedersen , O , Albrechtsen , A , Hansen , T & Grarup , N 2018 , ' Genetic determinants of glycated hemoglobin levels in the Greenlandic Inuit population ' , European Journal of Human Genetics , vol. 26 , no. 6 , pp. 868-875 . https://doi.org/10.1038/s41431-018-0109-3 Ankyrins/genetics Asian Continental Ancestry Group/genetics Blood Glucose/genetics Diabetes Mellitus Type 2/blood Ethnic Groups/genetics European Continental Ancestry Group Female Genetic Association Studies Genetic Predisposition to Disease Genetic Variation Genotype Glycated Hemoglobin A/genetics Greenland Humans Inuits/genetics Male Middle Aged Protein-Serine-Threonine Kinases/genetics article 2018 ftsydanskunivpub https://doi.org/10.1038/s41431-018-0109-3 2024-06-04T14:47:44Z We previously showed that a common genetic variant leads to a remarkably increased risk of type 2 diabetes (T2D) in the small and historically isolated Greenlandic population. Motivated by this, we aimed at discovering novel genetic determinants for glycated hemoglobin (HbA 1C) and at estimating the effect of known HbA 1C-associated loci in the Greenlandic population. We analyzed genotype data from 4049 Greenlanders generated using the Illumina Cardio-Metabochip. We performed the discovery association analysis by an additive linear mixed model. To estimate the effect of known HbA 1C-associated loci, we modeled the effect in the European and Inuit ancestry proportions of the Greenlandic genome (EAPGG and IAPGG, respectively). After correcting for multiple testing, we found no novel significant associations. When we investigated loci known to associate with HbA 1C levels, we found that the lead variant in the GCK locus associated significantly with HbA 1C levels in the IAPGG ([Formula: see text]). Furthermore, for 10 of 15 known HbA 1C loci, the effects in IAPGG were similar to the previously reported effects. Interestingly, the ANK1 locus showed a statistically significant ancestral population differential effect, with opposing directions of effect in the two ancestral populations. In conclusion, we found only 1 of the 15 known HbA 1C loci to be significantly associated with HbA 1C levels in the IAPGG and that two-thirds of the loci showed similar effects in Inuit as previously found in European and East Asian populations. Our results shed light on the genetic effects across ethnicities. Article in Journal/Newspaper Greenland greenlander* greenlandic inuit inuits University of Southern Denmark Research Portal Greenland European Journal of Human Genetics 26 6 868 875 |
institution |
Open Polar |
collection |
University of Southern Denmark Research Portal |
op_collection_id |
ftsydanskunivpub |
language |
English |
topic |
Ankyrins/genetics Asian Continental Ancestry Group/genetics Blood Glucose/genetics Diabetes Mellitus Type 2/blood Ethnic Groups/genetics European Continental Ancestry Group Female Genetic Association Studies Genetic Predisposition to Disease Genetic Variation Genotype Glycated Hemoglobin A/genetics Greenland Humans Inuits/genetics Male Middle Aged Protein-Serine-Threonine Kinases/genetics |
spellingShingle |
Ankyrins/genetics Asian Continental Ancestry Group/genetics Blood Glucose/genetics Diabetes Mellitus Type 2/blood Ethnic Groups/genetics European Continental Ancestry Group Female Genetic Association Studies Genetic Predisposition to Disease Genetic Variation Genotype Glycated Hemoglobin A/genetics Greenland Humans Inuits/genetics Male Middle Aged Protein-Serine-Threonine Kinases/genetics Appel, Emil V.R. Moltke, Ida Jørgensen, Marit E. Bjerregaard, Peter Linneberg, Allan Pedersen, Oluf Albrechtsen, Anders Hansen, Torben Grarup, Niels Genetic determinants of glycated hemoglobin levels in the Greenlandic Inuit population |
topic_facet |
Ankyrins/genetics Asian Continental Ancestry Group/genetics Blood Glucose/genetics Diabetes Mellitus Type 2/blood Ethnic Groups/genetics European Continental Ancestry Group Female Genetic Association Studies Genetic Predisposition to Disease Genetic Variation Genotype Glycated Hemoglobin A/genetics Greenland Humans Inuits/genetics Male Middle Aged Protein-Serine-Threonine Kinases/genetics |
description |
We previously showed that a common genetic variant leads to a remarkably increased risk of type 2 diabetes (T2D) in the small and historically isolated Greenlandic population. Motivated by this, we aimed at discovering novel genetic determinants for glycated hemoglobin (HbA 1C) and at estimating the effect of known HbA 1C-associated loci in the Greenlandic population. We analyzed genotype data from 4049 Greenlanders generated using the Illumina Cardio-Metabochip. We performed the discovery association analysis by an additive linear mixed model. To estimate the effect of known HbA 1C-associated loci, we modeled the effect in the European and Inuit ancestry proportions of the Greenlandic genome (EAPGG and IAPGG, respectively). After correcting for multiple testing, we found no novel significant associations. When we investigated loci known to associate with HbA 1C levels, we found that the lead variant in the GCK locus associated significantly with HbA 1C levels in the IAPGG ([Formula: see text]). Furthermore, for 10 of 15 known HbA 1C loci, the effects in IAPGG were similar to the previously reported effects. Interestingly, the ANK1 locus showed a statistically significant ancestral population differential effect, with opposing directions of effect in the two ancestral populations. In conclusion, we found only 1 of the 15 known HbA 1C loci to be significantly associated with HbA 1C levels in the IAPGG and that two-thirds of the loci showed similar effects in Inuit as previously found in European and East Asian populations. Our results shed light on the genetic effects across ethnicities. |
format |
Article in Journal/Newspaper |
author |
Appel, Emil V.R. Moltke, Ida Jørgensen, Marit E. Bjerregaard, Peter Linneberg, Allan Pedersen, Oluf Albrechtsen, Anders Hansen, Torben Grarup, Niels |
author_facet |
Appel, Emil V.R. Moltke, Ida Jørgensen, Marit E. Bjerregaard, Peter Linneberg, Allan Pedersen, Oluf Albrechtsen, Anders Hansen, Torben Grarup, Niels |
author_sort |
Appel, Emil V.R. |
title |
Genetic determinants of glycated hemoglobin levels in the Greenlandic Inuit population |
title_short |
Genetic determinants of glycated hemoglobin levels in the Greenlandic Inuit population |
title_full |
Genetic determinants of glycated hemoglobin levels in the Greenlandic Inuit population |
title_fullStr |
Genetic determinants of glycated hemoglobin levels in the Greenlandic Inuit population |
title_full_unstemmed |
Genetic determinants of glycated hemoglobin levels in the Greenlandic Inuit population |
title_sort |
genetic determinants of glycated hemoglobin levels in the greenlandic inuit population |
publishDate |
2018 |
url |
https://portal.findresearcher.sdu.dk/da/publications/3c4858f2-8fcd-4fcc-907b-95ed153add3e https://doi.org/10.1038/s41431-018-0109-3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974304/pdf/41431_2018_Article_109.pdf |
geographic |
Greenland |
geographic_facet |
Greenland |
genre |
Greenland greenlander* greenlandic inuit inuits |
genre_facet |
Greenland greenlander* greenlandic inuit inuits |
op_source |
Appel , E V R , Moltke , I , Jørgensen , M E , Bjerregaard , P , Linneberg , A , Pedersen , O , Albrechtsen , A , Hansen , T & Grarup , N 2018 , ' Genetic determinants of glycated hemoglobin levels in the Greenlandic Inuit population ' , European Journal of Human Genetics , vol. 26 , no. 6 , pp. 868-875 . https://doi.org/10.1038/s41431-018-0109-3 |
op_relation |
https://portal.findresearcher.sdu.dk/da/publications/3c4858f2-8fcd-4fcc-907b-95ed153add3e |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1038/s41431-018-0109-3 |
container_title |
European Journal of Human Genetics |
container_volume |
26 |
container_issue |
6 |
container_start_page |
868 |
op_container_end_page |
875 |
_version_ |
1802645027988439040 |