América Liliana Miranda-Lora1, Jenny Vilchis-Gil1, Daniel B Juárez-Comboni2, Miguel Cruz3, Miguel Klünder-Klünder4. 1. Epidemiological Research Unit in Endocrinology and Nutrition, Hospital Infantil de México Federico Gómez, Mexico City, Mexico. 2. Pediatric Medical Residency, Hospital Infantil de México Federico Gómez, Mexico City, Mexico. 3. Medical Research Unit in Biochemistry, Hospital de Especialidades Centro Médico Nacional SXXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico. 4. Research Subdirectorate, Hospital Infantil de México Federico Gómez, Mexico City, Mexico.
Abstract
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.
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.
Authors: Irina A Dubinina; Dimitry A Chistiakov; Irina A Eremina; Alexei N Brovkin; Lyubov I Zilberman; Alexei G Nikitin; Tamara L Kuraeva; Valery V Nosikov; Valentina A Peterkova; Ivan I Dedov Journal: Diabetes Metab Syndr Date: 2014-08-07
Authors: Ming Ding; Shafqat Ahmad; Lu Qi; Yang Hu; Shilpa N Bhupathiraju; Marta Guasch-Ferré; Majken K Jensen; Jorge E Chavarro; Paul M Ridker; Walter C Willett; Daniel I Chasman; Frank B Hu; Peter Kraft Journal: Am J Epidemiol Date: 2020-05-05 Impact factor: 4.897
Authors: J Tuomilehto; J Lindström; J G Eriksson; T T Valle; H Hämäläinen; P Ilanne-Parikka; S Keinänen-Kiukaanniemi; M Laakso; A Louheranta; M Rastas; V Salminen; M Uusitupa Journal: N Engl J Med Date: 2001-05-03 Impact factor: 91.245
Authors: Kyle J Gaulton; Teresa Ferreira; Yeji Lee; Anne Raimondo; Reedik Mägi; Michael E Reschen; Anubha Mahajan; Adam Locke; N William Rayner; Neil Robertson; Robert A Scott; Inga Prokopenko; Laura J Scott; Todd Green; Thomas Sparso; Dorothee Thuillier; Loic Yengo; Harald Grallert; Simone Wahl; Mattias Frånberg; Rona J Strawbridge; Hans Kestler; Himanshu Chheda; Lewin Eisele; Stefan Gustafsson; Valgerdur Steinthorsdottir; Gudmar Thorleifsson; Lu Qi; Lennart C Karssen; Elisabeth M van Leeuwen; Sara M Willems; Man Li; Han Chen; Christian Fuchsberger; Phoenix Kwan; Clement Ma; Michael Linderman; Yingchang Lu; Soren K Thomsen; Jana K Rundle; Nicola L Beer; Martijn van de Bunt; Anil Chalisey; Hyun Min Kang; Benjamin F Voight; Gonçalo R Abecasis; Peter Almgren; Damiano Baldassarre; Beverley Balkau; Rafn Benediktsson; Matthias Blüher; Heiner Boeing; Lori L Bonnycastle; Erwin P Bottinger; Noël P Burtt; Jason Carey; Guillaume Charpentier; Peter S Chines; Marilyn C Cornelis; David J Couper; Andrew T Crenshaw; Rob M van Dam; Alex S F Doney; Mozhgan Dorkhan; Sarah Edkins; Johan G Eriksson; Tonu Esko; Elodie Eury; João Fadista; Jason Flannick; Pierre Fontanillas; Caroline Fox; Paul W Franks; Karl Gertow; Christian Gieger; Bruna Gigante; Omri Gottesman; George B Grant; Niels Grarup; Christopher J Groves; Maija Hassinen; Christian T Have; Christian Herder; Oddgeir L Holmen; Astradur B Hreidarsson; Steve E Humphries; David J Hunter; Anne U Jackson; Anna Jonsson; Marit E Jørgensen; Torben Jørgensen; Wen-Hong L Kao; Nicola D Kerrison; Leena Kinnunen; Norman Klopp; Augustine Kong; Peter Kovacs; Peter Kraft; Jasmina Kravic; Cordelia Langford; Karin Leander; Liming Liang; Peter Lichtner; Cecilia M Lindgren; Eero Lindholm; Allan Linneberg; Ching-Ti Liu; Stéphane Lobbens; Jian'an Luan; Valeriya Lyssenko; Satu Männistö; Olga McLeod; Julia Meyer; Evelin Mihailov; Ghazala Mirza; Thomas W Mühleisen; Martina Müller-Nurasyid; Carmen Navarro; Markus M Nöthen; Nikolay N Oskolkov; Katharine R Owen; Domenico Palli; Sonali Pechlivanis; Leena Peltonen; John R B Perry; Carl G P Platou; Michael Roden; Douglas Ruderfer; Denis Rybin; Yvonne T van der Schouw; Bengt Sennblad; Gunnar Sigurðsson; Alena Stančáková; Gerald Steinbach; Petter Storm; Konstantin Strauch; Heather M Stringham; Qi Sun; Barbara Thorand; Emmi Tikkanen; Anke Tonjes; Joseph Trakalo; Elena Tremoli; Tiinamaija Tuomi; Roman Wennauer; Steven Wiltshire; Andrew R Wood; Eleftheria Zeggini; Ian Dunham; Ewan Birney; Lorenzo Pasquali; Jorge Ferrer; Ruth J F Loos; Josée Dupuis; Jose C Florez; Eric Boerwinkle; James S Pankow; Cornelia van Duijn; Eric Sijbrands; James B Meigs; Frank B Hu; Unnur Thorsteinsdottir; Kari Stefansson; Timo A Lakka; Rainer Rauramaa; Michael Stumvoll; Nancy L Pedersen; Lars Lind; Sirkka M Keinanen-Kiukaanniemi; Eeva Korpi-Hyövälti; Timo E Saaristo; Juha Saltevo; Johanna Kuusisto; Markku Laakso; Andres Metspalu; Raimund Erbel; Karl-Heinz Jöcke; Susanne Moebus; Samuli Ripatti; Veikko Salomaa; Erik Ingelsson; Bernhard O Boehm; Richard N Bergman; Francis S Collins; Karen L Mohlke; Heikki Koistinen; Jaakko Tuomilehto; Kristian Hveem; Inger Njølstad; Panagiotis Deloukas; Peter J Donnelly; Timothy M Frayling; Andrew T Hattersley; Ulf de Faire; Anders Hamsten; Thomas Illig; Annette Peters; Stephane Cauchi; Rob Sladek; Philippe Froguel; Torben Hansen; Oluf Pedersen; Andrew D Morris; Collin N A Palmer; Sekar Kathiresan; Olle Melander; Peter M Nilsson; Leif C Groop; Inês Barroso; Claudia Langenberg; Nicholas J Wareham; Christopher A O'Callaghan; Anna L Gloyn; David Altshuler; Michael Boehnke; Tanya M Teslovich; Mark I McCarthy; Andrew P Morris Journal: Nat Genet Date: 2015-11-09 Impact factor: 38.330