Genetic associations in community context: a mixed model approach identifies a functional variant in the RBP4 gene associated with HDL-C dyslipidemia
Abstract Background The objective of this study was to examine individual and community factors that influence high-density lipoprotein cholesterol (HDL-C) dyslipidemia in Newfoundland and Labrador (NL), a genetically isolated population in Canada with a high prevalence of HDL-C dyslipidemia. Method...
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ftdoajarticles:oai:doaj.org/article:86bb12eefe7e46e2a3413386b26e99aa 2023-05-15T17:22:48+02:00 Genetic associations in community context: a mixed model approach identifies a functional variant in the RBP4 gene associated with HDL-C dyslipidemia Erfan Aref-Eshghi Oliver Hurley Guang Sun Alvin Simms Marshall Godwin Pauline Duke Mehdee Araee Masoud Mahdavian Shabnam Asghari 2018-11-01T00:00:00Z https://doi.org/10.1186/s12881-018-0719-1 https://doaj.org/article/86bb12eefe7e46e2a3413386b26e99aa EN eng BMC http://link.springer.com/article/10.1186/s12881-018-0719-1 https://doaj.org/toc/1471-2350 doi:10.1186/s12881-018-0719-1 1471-2350 https://doaj.org/article/86bb12eefe7e46e2a3413386b26e99aa BMC Medical Genetics, Vol 19, Iss 1, Pp 1-9 (2018) HDL Dyslipidemia RBP4 Mixed model Genetics Associations Internal medicine RC31-1245 QH426-470 article 2018 ftdoajarticles https://doi.org/10.1186/s12881-018-0719-1 2022-12-31T06:41:31Z Abstract Background The objective of this study was to examine individual and community factors that influence high-density lipoprotein cholesterol (HDL-C) dyslipidemia in Newfoundland and Labrador (NL), a genetically isolated population in Canada with a high prevalence of HDL-C dyslipidemia. Methods First, a group of single nucleotide polymorphisms from 10 metabolic trait candidate genes was tested using a multivariate logistic regression model. The significant SNPs were entered into the second phase, where a mixed logistic model incorporated the community disease risk factors together with the individual factors as the fixed part of the model and the geographic region as a random effect. Results Analysis of 1489 subjects (26.9% HDL-C dyslipidemia) identified rs3758539, a non-coding variant in the 5’UTR of RBP4, to be associated with HDL-C dyslipidemia (odds ratio = 1.45, 95% confidence interval = 1.08–1.97, p = 0.01). The association remained significant, and the effect size did not change after the incorporation of individual and community risk factors from 17 geographic regions (odds ratio: 1.41, 95% confidence interval = 1.03–1.93, p = 0.03) in NL. Besides this variant, sex, BMI, and smoking also showed significant associations with HDL-C dyslipidemia, whereas no role was identified for the community factors. Conclusions This study demonstrates the use of community-level data in a genetic association testing. It reports a functional variant in the promoter of RBP4, a gene directly involved in lipoprotein metabolism, to be associated with HDL-C dyslipidemia. These findings indicate that individual factors are the main reason for a higher prevalence of HDL-C dyslipidemia in the NL population. Article in Journal/Newspaper Newfoundland Directory of Open Access Journals: DOAJ Articles Newfoundland Canada BMC Medical Genetics 19 1 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
HDL Dyslipidemia RBP4 Mixed model Genetics Associations Internal medicine RC31-1245 QH426-470 |
spellingShingle |
HDL Dyslipidemia RBP4 Mixed model Genetics Associations Internal medicine RC31-1245 QH426-470 Erfan Aref-Eshghi Oliver Hurley Guang Sun Alvin Simms Marshall Godwin Pauline Duke Mehdee Araee Masoud Mahdavian Shabnam Asghari Genetic associations in community context: a mixed model approach identifies a functional variant in the RBP4 gene associated with HDL-C dyslipidemia |
topic_facet |
HDL Dyslipidemia RBP4 Mixed model Genetics Associations Internal medicine RC31-1245 QH426-470 |
description |
Abstract Background The objective of this study was to examine individual and community factors that influence high-density lipoprotein cholesterol (HDL-C) dyslipidemia in Newfoundland and Labrador (NL), a genetically isolated population in Canada with a high prevalence of HDL-C dyslipidemia. Methods First, a group of single nucleotide polymorphisms from 10 metabolic trait candidate genes was tested using a multivariate logistic regression model. The significant SNPs were entered into the second phase, where a mixed logistic model incorporated the community disease risk factors together with the individual factors as the fixed part of the model and the geographic region as a random effect. Results Analysis of 1489 subjects (26.9% HDL-C dyslipidemia) identified rs3758539, a non-coding variant in the 5’UTR of RBP4, to be associated with HDL-C dyslipidemia (odds ratio = 1.45, 95% confidence interval = 1.08–1.97, p = 0.01). The association remained significant, and the effect size did not change after the incorporation of individual and community risk factors from 17 geographic regions (odds ratio: 1.41, 95% confidence interval = 1.03–1.93, p = 0.03) in NL. Besides this variant, sex, BMI, and smoking also showed significant associations with HDL-C dyslipidemia, whereas no role was identified for the community factors. Conclusions This study demonstrates the use of community-level data in a genetic association testing. It reports a functional variant in the promoter of RBP4, a gene directly involved in lipoprotein metabolism, to be associated with HDL-C dyslipidemia. These findings indicate that individual factors are the main reason for a higher prevalence of HDL-C dyslipidemia in the NL population. |
format |
Article in Journal/Newspaper |
author |
Erfan Aref-Eshghi Oliver Hurley Guang Sun Alvin Simms Marshall Godwin Pauline Duke Mehdee Araee Masoud Mahdavian Shabnam Asghari |
author_facet |
Erfan Aref-Eshghi Oliver Hurley Guang Sun Alvin Simms Marshall Godwin Pauline Duke Mehdee Araee Masoud Mahdavian Shabnam Asghari |
author_sort |
Erfan Aref-Eshghi |
title |
Genetic associations in community context: a mixed model approach identifies a functional variant in the RBP4 gene associated with HDL-C dyslipidemia |
title_short |
Genetic associations in community context: a mixed model approach identifies a functional variant in the RBP4 gene associated with HDL-C dyslipidemia |
title_full |
Genetic associations in community context: a mixed model approach identifies a functional variant in the RBP4 gene associated with HDL-C dyslipidemia |
title_fullStr |
Genetic associations in community context: a mixed model approach identifies a functional variant in the RBP4 gene associated with HDL-C dyslipidemia |
title_full_unstemmed |
Genetic associations in community context: a mixed model approach identifies a functional variant in the RBP4 gene associated with HDL-C dyslipidemia |
title_sort |
genetic associations in community context: a mixed model approach identifies a functional variant in the rbp4 gene associated with hdl-c dyslipidemia |
publisher |
BMC |
publishDate |
2018 |
url |
https://doi.org/10.1186/s12881-018-0719-1 https://doaj.org/article/86bb12eefe7e46e2a3413386b26e99aa |
geographic |
Newfoundland Canada |
geographic_facet |
Newfoundland Canada |
genre |
Newfoundland |
genre_facet |
Newfoundland |
op_source |
BMC Medical Genetics, Vol 19, Iss 1, Pp 1-9 (2018) |
op_relation |
http://link.springer.com/article/10.1186/s12881-018-0719-1 https://doaj.org/toc/1471-2350 doi:10.1186/s12881-018-0719-1 1471-2350 https://doaj.org/article/86bb12eefe7e46e2a3413386b26e99aa |
op_doi |
https://doi.org/10.1186/s12881-018-0719-1 |
container_title |
BMC Medical Genetics |
container_volume |
19 |
container_issue |
1 |
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1766109657833668608 |