The combined effects of FADS gene variation and dietary fats in obesity-related traits in a population from the far north of Sweden : the GLACIER Study
BACKGROUND: Recent analyses in Greenlandic Inuit identified six genetic polymorphisms (rs74771917, rs3168072, rs12577276, rs7115739, rs174602 and rs174570) in the fatty acid desaturase gene cluster (FADS1-FADS2-FADS3) that are associated with multiple metabolic and anthropometric traits. Our objecti...
Published in: | International Journal of Obesity |
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Umeå universitet, Enheten för biobanksforskning
2019
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Online Access: | http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-158784 https://doi.org/10.1038/s41366-018-0112-3 |
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ftumeauniv:oai:DiVA.org:umu-158784 2023-10-09T21:52:06+02:00 The combined effects of FADS gene variation and dietary fats in obesity-related traits in a population from the far north of Sweden : the GLACIER Study Chen, Yan Estampador, Angela C Keller, Maria Poveda, Alaitz Dalla-Riva, Jonathan Johansson, Ingegerd Renström, Frida Kurbasic, Azra Franks, Paul W. Varga, Tibor V 2019 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-158784 https://doi.org/10.1038/s41366-018-0112-3 eng eng Umeå universitet, Enheten för biobanksforskning Umeå universitet, Avdelningen för medicin Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Skåne University Hospital Malmö, Malmö, Sweden Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Skåne University Hospital Malmö, Malmö, Sweden; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston MA, USA International Journal of Obesity, 0307-0565, 2019, 43:4, s. 808-820 orcid:0000-0002-9227-8434 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-158784 doi:10.1038/s41366-018-0112-3 PMID 29795460 ISI:000462994400019 Scopus 2-s2.0-85047367345 info:eu-repo/semantics/openAccess Nutrition and Dietetics Näringslära Article in journal info:eu-repo/semantics/article text 2019 ftumeauniv https://doi.org/10.1038/s41366-018-0112-3 2023-09-22T13:58:53Z BACKGROUND: Recent analyses in Greenlandic Inuit identified six genetic polymorphisms (rs74771917, rs3168072, rs12577276, rs7115739, rs174602 and rs174570) in the fatty acid desaturase gene cluster (FADS1-FADS2-FADS3) that are associated with multiple metabolic and anthropometric traits. Our objectives were to systematically assess whether dietary polyunsaturated fatty acid (PUFA) intake modifies the associations between genetic variants in the FADS gene cluster and cardiometabolic traits, and to functionally annotate top-ranking candidates to estimate their regulatory potential. METHODS: Data analyses consisted of the following: interaction analyses between the 6 candidate genetic variants and dietary PUFA intake; gene-centric joint analyses to detect interaction signals in the FADS region; haplotype-centric joint tests across 30 haplotype blocks in the FADS region to refine interaction signals; and functional annotation of top-ranking loci from the previous steps. These analyses were undertaken in Swedish adults from the GLACIER Study (N = 5,160); data on genetic variation and eight cardiometabolic traits were used. RESULTS: Interactions were observed between rs174570 and n-6 PUFA intake on fasting glucose (Pint = 0.005) and between rs174602 and n-3 PUFA intake on total cholesterol (Pint = 0.001). Gene-centric analyses demonstrated a statistically significant interaction effect for FADS and n-3 PUFA on triglycerides (Pint = 0.005) considering genetic main effects as random. Haplotype analyses revealed three blocks (Pint < 0.011) that could drive the interaction between FADS and n-3 PUFA on triglycerides; functional annotation of these regions showed that each block harbours a number of highly functional regulatory variants; FADS2 rs5792235 demonstrated the highest functionality score. CONCLUSIONS: The association between FADS variants and triglycerides may be modified by PUFA intake. The intronic FADS2 rs5792235 variant is a potential causal variant in the region, having the highest regulatory potential. ... Article in Journal/Newspaper greenlandic inuit Umeå University: Publications (DiVA) International Journal of Obesity 43 4 808 820 |
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Open Polar |
collection |
Umeå University: Publications (DiVA) |
op_collection_id |
ftumeauniv |
language |
English |
topic |
Nutrition and Dietetics Näringslära |
spellingShingle |
Nutrition and Dietetics Näringslära Chen, Yan Estampador, Angela C Keller, Maria Poveda, Alaitz Dalla-Riva, Jonathan Johansson, Ingegerd Renström, Frida Kurbasic, Azra Franks, Paul W. Varga, Tibor V The combined effects of FADS gene variation and dietary fats in obesity-related traits in a population from the far north of Sweden : the GLACIER Study |
topic_facet |
Nutrition and Dietetics Näringslära |
description |
BACKGROUND: Recent analyses in Greenlandic Inuit identified six genetic polymorphisms (rs74771917, rs3168072, rs12577276, rs7115739, rs174602 and rs174570) in the fatty acid desaturase gene cluster (FADS1-FADS2-FADS3) that are associated with multiple metabolic and anthropometric traits. Our objectives were to systematically assess whether dietary polyunsaturated fatty acid (PUFA) intake modifies the associations between genetic variants in the FADS gene cluster and cardiometabolic traits, and to functionally annotate top-ranking candidates to estimate their regulatory potential. METHODS: Data analyses consisted of the following: interaction analyses between the 6 candidate genetic variants and dietary PUFA intake; gene-centric joint analyses to detect interaction signals in the FADS region; haplotype-centric joint tests across 30 haplotype blocks in the FADS region to refine interaction signals; and functional annotation of top-ranking loci from the previous steps. These analyses were undertaken in Swedish adults from the GLACIER Study (N = 5,160); data on genetic variation and eight cardiometabolic traits were used. RESULTS: Interactions were observed between rs174570 and n-6 PUFA intake on fasting glucose (Pint = 0.005) and between rs174602 and n-3 PUFA intake on total cholesterol (Pint = 0.001). Gene-centric analyses demonstrated a statistically significant interaction effect for FADS and n-3 PUFA on triglycerides (Pint = 0.005) considering genetic main effects as random. Haplotype analyses revealed three blocks (Pint < 0.011) that could drive the interaction between FADS and n-3 PUFA on triglycerides; functional annotation of these regions showed that each block harbours a number of highly functional regulatory variants; FADS2 rs5792235 demonstrated the highest functionality score. CONCLUSIONS: The association between FADS variants and triglycerides may be modified by PUFA intake. The intronic FADS2 rs5792235 variant is a potential causal variant in the region, having the highest regulatory potential. ... |
format |
Article in Journal/Newspaper |
author |
Chen, Yan Estampador, Angela C Keller, Maria Poveda, Alaitz Dalla-Riva, Jonathan Johansson, Ingegerd Renström, Frida Kurbasic, Azra Franks, Paul W. Varga, Tibor V |
author_facet |
Chen, Yan Estampador, Angela C Keller, Maria Poveda, Alaitz Dalla-Riva, Jonathan Johansson, Ingegerd Renström, Frida Kurbasic, Azra Franks, Paul W. Varga, Tibor V |
author_sort |
Chen, Yan |
title |
The combined effects of FADS gene variation and dietary fats in obesity-related traits in a population from the far north of Sweden : the GLACIER Study |
title_short |
The combined effects of FADS gene variation and dietary fats in obesity-related traits in a population from the far north of Sweden : the GLACIER Study |
title_full |
The combined effects of FADS gene variation and dietary fats in obesity-related traits in a population from the far north of Sweden : the GLACIER Study |
title_fullStr |
The combined effects of FADS gene variation and dietary fats in obesity-related traits in a population from the far north of Sweden : the GLACIER Study |
title_full_unstemmed |
The combined effects of FADS gene variation and dietary fats in obesity-related traits in a population from the far north of Sweden : the GLACIER Study |
title_sort |
combined effects of fads gene variation and dietary fats in obesity-related traits in a population from the far north of sweden : the glacier study |
publisher |
Umeå universitet, Enheten för biobanksforskning |
publishDate |
2019 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-158784 https://doi.org/10.1038/s41366-018-0112-3 |
genre |
greenlandic inuit |
genre_facet |
greenlandic inuit |
op_relation |
International Journal of Obesity, 0307-0565, 2019, 43:4, s. 808-820 orcid:0000-0002-9227-8434 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-158784 doi:10.1038/s41366-018-0112-3 PMID 29795460 ISI:000462994400019 Scopus 2-s2.0-85047367345 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1038/s41366-018-0112-3 |
container_title |
International Journal of Obesity |
container_volume |
43 |
container_issue |
4 |
container_start_page |
808 |
op_container_end_page |
820 |
_version_ |
1779315230813192192 |