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A Genetic Risk Score Improves the Prediction of Type 2 Diabetes Mellitus in Mexican Youths but Has Lower Predictive Utility Compared With Non-Genetic Factors

BACKGROUND: Type 2 diabetes (T2D) is a multifactorial disease caused by a complex interplay between environmental risk factors and genetic predisposition. To date, a total of 10 single nucleotide polymorphism (SNPs) have been associated with pediatric-onset T2D in Mexicans, with a small individual e...

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Autores principales: Miranda-Lora, América Liliana, Vilchis-Gil, Jenny, Juárez-Comboni, Daniel B., Cruz, Miguel, Klünder-Klünder, Miguel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994893/
https://www.ncbi.nlm.nih.gov/pubmed/33776940
http://dx.doi.org/10.3389/fendo.2021.647864
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author Miranda-Lora, América Liliana
Vilchis-Gil, Jenny
Juárez-Comboni, Daniel B.
Cruz, Miguel
Klünder-Klünder, Miguel
author_facet Miranda-Lora, América Liliana
Vilchis-Gil, Jenny
Juárez-Comboni, Daniel B.
Cruz, Miguel
Klünder-Klünder, Miguel
author_sort Miranda-Lora, América Liliana
collection PubMed
description BACKGROUND: Type 2 diabetes (T2D) is a multifactorial disease caused by a complex interplay between environmental risk factors and genetic predisposition. To date, a total of 10 single nucleotide polymorphism (SNPs) have been associated with pediatric-onset T2D in Mexicans, with a small individual effect size. A genetic risk score (GRS) that combines these SNPs could serve as a predictor of the risk for pediatric-onset T2D. OBJECTIVE: To assess the clinical utility of a GRS that combines 10 SNPs to improve risk prediction of pediatric-onset T2D in Mexicans. METHODS: This case-control study included 97 individuals with pediatric-onset T2D and 84 controls below 18 years old without T2D. Information regarding family history of T2D, demographics, perinatal risk factors, anthropometric measurements, biochemical variables, lifestyle, and fitness scores were then obtained. Moreover, 10 single nucleotide polymorphisms (SNPs) previously associated with pediatric-onset T2D in Mexicans were genotyped. The GRS was calculated by summing the 10 risk alleles. Pediatric-onset T2D risk variance was assessed using multivariable logistic regression models and the area under the receiver operating characteristic curve (AUC). RESULTS: The body mass index Z-score (Z-BMI) [odds ratio (OR) = 1.7; p = 0.009] and maternal history of T2D (OR = 7.1; p < 0.001) were found to be independently associated with pediatric-onset T2D. No association with other clinical risk factors was observed. The GRS also showed a significant association with pediatric-onset T2D (OR = 1.3 per risk allele; p = 0.006). The GRS, clinical risk factors, and GRS plus clinical risk factors had an AUC of 0.66 (95% CI 0.56–0.75), 0.72 (95% CI 0.62–0.81), and 0.78 (95% CI 0.70–0.87), respectively (p < 0.01). CONCLUSION: The GRS based on 10 SNPs was associated with pediatric-onset T2D in Mexicans and improved its prediction with modest significance. However, clinical factors, such the Z-BMI and family history of T2D, continue to have the highest predictive utility in this population.
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spelling pubmed-79948932021-03-27 A Genetic Risk Score Improves the Prediction of Type 2 Diabetes Mellitus in Mexican Youths but Has Lower Predictive Utility Compared With Non-Genetic Factors Miranda-Lora, América Liliana Vilchis-Gil, Jenny Juárez-Comboni, Daniel B. Cruz, Miguel Klünder-Klünder, Miguel Front Endocrinol (Lausanne) Endocrinology BACKGROUND: Type 2 diabetes (T2D) is a multifactorial disease caused by a complex interplay between environmental risk factors and genetic predisposition. To date, a total of 10 single nucleotide polymorphism (SNPs) have been associated with pediatric-onset T2D in Mexicans, with a small individual effect size. A genetic risk score (GRS) that combines these SNPs could serve as a predictor of the risk for pediatric-onset T2D. OBJECTIVE: To assess the clinical utility of a GRS that combines 10 SNPs to improve risk prediction of pediatric-onset T2D in Mexicans. METHODS: This case-control study included 97 individuals with pediatric-onset T2D and 84 controls below 18 years old without T2D. Information regarding family history of T2D, demographics, perinatal risk factors, anthropometric measurements, biochemical variables, lifestyle, and fitness scores were then obtained. Moreover, 10 single nucleotide polymorphisms (SNPs) previously associated with pediatric-onset T2D in Mexicans were genotyped. The GRS was calculated by summing the 10 risk alleles. Pediatric-onset T2D risk variance was assessed using multivariable logistic regression models and the area under the receiver operating characteristic curve (AUC). RESULTS: The body mass index Z-score (Z-BMI) [odds ratio (OR) = 1.7; p = 0.009] and maternal history of T2D (OR = 7.1; p < 0.001) were found to be independently associated with pediatric-onset T2D. No association with other clinical risk factors was observed. The GRS also showed a significant association with pediatric-onset T2D (OR = 1.3 per risk allele; p = 0.006). The GRS, clinical risk factors, and GRS plus clinical risk factors had an AUC of 0.66 (95% CI 0.56–0.75), 0.72 (95% CI 0.62–0.81), and 0.78 (95% CI 0.70–0.87), respectively (p < 0.01). CONCLUSION: The GRS based on 10 SNPs was associated with pediatric-onset T2D in Mexicans and improved its prediction with modest significance. However, clinical factors, such the Z-BMI and family history of T2D, continue to have the highest predictive utility in this population. Frontiers Media S.A. 2021-03-12 /pmc/articles/PMC7994893/ /pubmed/33776940 http://dx.doi.org/10.3389/fendo.2021.647864 Text en Copyright © 2021 Miranda-Lora, Vilchis-Gil, Juárez-Comboni, Cruz and Klünder-Klünder http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Miranda-Lora, América Liliana
Vilchis-Gil, Jenny
Juárez-Comboni, Daniel B.
Cruz, Miguel
Klünder-Klünder, Miguel
A Genetic Risk Score Improves the Prediction of Type 2 Diabetes Mellitus in Mexican Youths but Has Lower Predictive Utility Compared With Non-Genetic Factors
title A Genetic Risk Score Improves the Prediction of Type 2 Diabetes Mellitus in Mexican Youths but Has Lower Predictive Utility Compared With Non-Genetic Factors
title_full A Genetic Risk Score Improves the Prediction of Type 2 Diabetes Mellitus in Mexican Youths but Has Lower Predictive Utility Compared With Non-Genetic Factors
title_fullStr A Genetic Risk Score Improves the Prediction of Type 2 Diabetes Mellitus in Mexican Youths but Has Lower Predictive Utility Compared With Non-Genetic Factors
title_full_unstemmed A Genetic Risk Score Improves the Prediction of Type 2 Diabetes Mellitus in Mexican Youths but Has Lower Predictive Utility Compared With Non-Genetic Factors
title_short A Genetic Risk Score Improves the Prediction of Type 2 Diabetes Mellitus in Mexican Youths but Has Lower Predictive Utility Compared With Non-Genetic Factors
title_sort genetic risk score improves the prediction of type 2 diabetes mellitus in mexican youths but has lower predictive utility compared with non-genetic factors
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994893/
https://www.ncbi.nlm.nih.gov/pubmed/33776940
http://dx.doi.org/10.3389/fendo.2021.647864
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