Effect of metabolic genetic variants on long-term disease comorbidity in patients with type 2 diabetes

Abstract Underlying genetic determinants contribute to developing type 2 diabetes (T2D) future diseases. The present study aimed to identify which genetic variants are associated with the incident of the major T2D co-morbid disease. First, we conducted a discovery study by investigating the genetic...

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Autores principales:	Shifteh Abedian, Ali Abbasi, Anthonius de Boer, Bruno H. Stricker, Stephan J. L. Bakker, Pim van der Harst, Sanaz Sedaghat, Maryam Darvishian, M. Arfan Ikram, Gerjan Navis, Abbas Dehghan, Ido Pen, Ronald P. Stolk, Harold Snieder, Olaf H. Klungel, Patrick Souverein, Behrooz Z. Alizadeh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aa3f7f248dec47f8937274ca6bd7824b
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spelling	oai:doaj.org-article:aa3f7f248dec47f8937274ca6bd7824b2021-12-02T14:06:55ZEffect of metabolic genetic variants on long-term disease comorbidity in patients with type 2 diabetes10.1038/s41598-021-82276-32045-2322https://doaj.org/article/aa3f7f248dec47f8937274ca6bd7824b2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82276-3https://doaj.org/toc/2045-2322Abstract Underlying genetic determinants contribute to developing type 2 diabetes (T2D) future diseases. The present study aimed to identify which genetic variants are associated with the incident of the major T2D co-morbid disease. First, we conducted a discovery study by investigating the genetic associations of comorbid diseases within the framework of the Utrecht Cardiovascular Pharmacogenetic studies by turning information of > 25 years follow-up data of 1237 subjects whom were genotyped and included in the discovery study. We performed Cox proportional-hazards regression to examine associations between genetic variants and comorbid diseases including cardiovascular diseases (CVD), chronic eye disease, cancer, neurologic diseases and chronic kidney disease. Secondly, we replicated our findings in two independent cohorts consisting of 1041 subjects. Finally, we performed a meta-analysis by combining the discovery and two replication cohorts. We ascertained 390 (39.7%) incident cases of CVD, 182 (16.2%) of chronic eye disease, 155 (13.8%) of cancer, 31 (2.7%) of neurologic disease and 13 (1.1%) of chronic kidney disease during a median follow-up of 10.2 years. In the discovery study, we identified a total of 39 Single Nucleotide Polymorphisms (SNPs) associated with comorbid diseases. The replication study, confirmed that rs1870849 and rs8051326 may play a role in the incidence of chronic eye disease in T2D patients. Half of patients developed at least one comorbid disease, with CVD occurring most often and earliest followed by chronic eye disease. Further research is needed to confirm the associations of two associated SNPs with chronic eye disease in T2D.Shifteh AbedianAli AbbasiAnthonius de BoerBruno H. StrickerStephan J. L. BakkerPim van der HarstSanaz SedaghatMaryam DarvishianM. Arfan IkramGerjan NavisAbbas DehghanIdo PenRonald P. StolkHarold SniederOlaf H. KlungelPatrick SouvereinBehrooz Z. AlizadehNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shifteh Abedian Ali Abbasi Anthonius de Boer Bruno H. Stricker Stephan J. L. Bakker Pim van der Harst Sanaz Sedaghat Maryam Darvishian M. Arfan Ikram Gerjan Navis Abbas Dehghan Ido Pen Ronald P. Stolk Harold Snieder Olaf H. Klungel Patrick Souverein Behrooz Z. Alizadeh Effect of metabolic genetic variants on long-term disease comorbidity in patients with type 2 diabetes
description	Abstract Underlying genetic determinants contribute to developing type 2 diabetes (T2D) future diseases. The present study aimed to identify which genetic variants are associated with the incident of the major T2D co-morbid disease. First, we conducted a discovery study by investigating the genetic associations of comorbid diseases within the framework of the Utrecht Cardiovascular Pharmacogenetic studies by turning information of > 25 years follow-up data of 1237 subjects whom were genotyped and included in the discovery study. We performed Cox proportional-hazards regression to examine associations between genetic variants and comorbid diseases including cardiovascular diseases (CVD), chronic eye disease, cancer, neurologic diseases and chronic kidney disease. Secondly, we replicated our findings in two independent cohorts consisting of 1041 subjects. Finally, we performed a meta-analysis by combining the discovery and two replication cohorts. We ascertained 390 (39.7%) incident cases of CVD, 182 (16.2%) of chronic eye disease, 155 (13.8%) of cancer, 31 (2.7%) of neurologic disease and 13 (1.1%) of chronic kidney disease during a median follow-up of 10.2 years. In the discovery study, we identified a total of 39 Single Nucleotide Polymorphisms (SNPs) associated with comorbid diseases. The replication study, confirmed that rs1870849 and rs8051326 may play a role in the incidence of chronic eye disease in T2D patients. Half of patients developed at least one comorbid disease, with CVD occurring most often and earliest followed by chronic eye disease. Further research is needed to confirm the associations of two associated SNPs with chronic eye disease in T2D.
format	article
author	Shifteh Abedian Ali Abbasi Anthonius de Boer Bruno H. Stricker Stephan J. L. Bakker Pim van der Harst Sanaz Sedaghat Maryam Darvishian M. Arfan Ikram Gerjan Navis Abbas Dehghan Ido Pen Ronald P. Stolk Harold Snieder Olaf H. Klungel Patrick Souverein Behrooz Z. Alizadeh
author_facet	Shifteh Abedian Ali Abbasi Anthonius de Boer Bruno H. Stricker Stephan J. L. Bakker Pim van der Harst Sanaz Sedaghat Maryam Darvishian M. Arfan Ikram Gerjan Navis Abbas Dehghan Ido Pen Ronald P. Stolk Harold Snieder Olaf H. Klungel Patrick Souverein Behrooz Z. Alizadeh
author_sort	Shifteh Abedian
title	Effect of metabolic genetic variants on long-term disease comorbidity in patients with type 2 diabetes
title_short	Effect of metabolic genetic variants on long-term disease comorbidity in patients with type 2 diabetes
title_full	Effect of metabolic genetic variants on long-term disease comorbidity in patients with type 2 diabetes
title_fullStr	Effect of metabolic genetic variants on long-term disease comorbidity in patients with type 2 diabetes
title_full_unstemmed	Effect of metabolic genetic variants on long-term disease comorbidity in patients with type 2 diabetes
title_sort	effect of metabolic genetic variants on long-term disease comorbidity in patients with type 2 diabetes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/aa3f7f248dec47f8937274ca6bd7824b
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Effect of metabolic genetic variants on long-term disease comorbidity in patients with type 2 diabetes

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