Use of net reclassification improvement (NRI) method confirms the utility of combined genetic risk score to predict type 2 diabetes.

<h4>Background</h4>Recent genome-wide association studies (GWAS) identified more than 70 novel loci for type 2 diabetes (T2D), some of which have been widely replicated in Asian populations. In this study, we investigated their individual and combined effects on T2D in a Chinese populati...

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Autores principales:	Claudia H T Tam, Janice S K Ho, Ying Wang, Vincent K L Lam, Heung Man Lee, Guozhi Jiang, Eric S H Lau, Alice P S Kong, Xiaodan Fan, Jean L F Woo, Stephen K W Tsui, Maggie C Y Ng, Wing Yee So, Juliana C N Chan, Ronald C W Ma
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/45e049b9d1db45278d2b5c787b41bf48
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spelling	oai:doaj.org-article:45e049b9d1db45278d2b5c787b41bf482021-11-18T08:40:56ZUse of net reclassification improvement (NRI) method confirms the utility of combined genetic risk score to predict type 2 diabetes.1932-620310.1371/journal.pone.0083093https://doaj.org/article/45e049b9d1db45278d2b5c787b41bf482013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24376643/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Recent genome-wide association studies (GWAS) identified more than 70 novel loci for type 2 diabetes (T2D), some of which have been widely replicated in Asian populations. In this study, we investigated their individual and combined effects on T2D in a Chinese population.<h4>Methodology</h4>We selected 14 single nucleotide polymorphisms (SNPs) in T2D genes relating to beta-cell function validated in Asian populations and genotyped them in 5882 Chinese T2D patients and 2569 healthy controls. A combined genetic score (CGS) was calculated by summing up the number of risk alleles or weighted by the effect size for each SNP under an additive genetic model. We tested for associations by either logistic or linear regression analysis for T2D and quantitative traits, respectively. The contribution of the CGS for predicting T2D risk was evaluated by receiver operating characteristic (ROC) analysis and net reclassification improvement (NRI).<h4>Results</h4>We observed consistent and significant associations of IGF2BP2, WFS1, CDKAL1, SLC30A8, CDKN2A/B, HHEX, TCF7L2 and KCNQ1 (8.5×10(-18)<P<8.5×10(-3)), as well as nominal associations of NOTCH2, JAZF1, KCNJ11 and HNF1B (0.05<P<0.1) with T2D risk, which yielded odds ratios ranging from 1.07 to 2.09. The 8 significant SNPs exhibited joint effect on increasing T2D risk, fasting plasma glucose and use of insulin therapy as well as reducing HOMA-β, BMI, waist circumference and younger age of diagnosis of T2D. The addition of CGS marginally increased AUC (2%) but significantly improved the predictive ability on T2D risk by 11.2% and 11.3% for unweighted and weighted CGS, respectively using the NRI approach (P<0.001).<h4>Conclusion</h4>In a Chinese population, the use of a CGS of 8 SNPs modestly but significantly improved its discriminative ability to predict T2D above and beyond that attributed to clinical risk factors (sex, age and BMI).Claudia H T TamJanice S K HoYing WangVincent K L LamHeung Man LeeGuozhi JiangEric S H LauAlice P S KongXiaodan FanJean L F WooStephen K W TsuiMaggie C Y NgWing Yee SoJuliana C N ChanRonald C W MaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e83093 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Claudia H T Tam Janice S K Ho Ying Wang Vincent K L Lam Heung Man Lee Guozhi Jiang Eric S H Lau Alice P S Kong Xiaodan Fan Jean L F Woo Stephen K W Tsui Maggie C Y Ng Wing Yee So Juliana C N Chan Ronald C W Ma Use of net reclassification improvement (NRI) method confirms the utility of combined genetic risk score to predict type 2 diabetes.
description	<h4>Background</h4>Recent genome-wide association studies (GWAS) identified more than 70 novel loci for type 2 diabetes (T2D), some of which have been widely replicated in Asian populations. In this study, we investigated their individual and combined effects on T2D in a Chinese population.<h4>Methodology</h4>We selected 14 single nucleotide polymorphisms (SNPs) in T2D genes relating to beta-cell function validated in Asian populations and genotyped them in 5882 Chinese T2D patients and 2569 healthy controls. A combined genetic score (CGS) was calculated by summing up the number of risk alleles or weighted by the effect size for each SNP under an additive genetic model. We tested for associations by either logistic or linear regression analysis for T2D and quantitative traits, respectively. The contribution of the CGS for predicting T2D risk was evaluated by receiver operating characteristic (ROC) analysis and net reclassification improvement (NRI).<h4>Results</h4>We observed consistent and significant associations of IGF2BP2, WFS1, CDKAL1, SLC30A8, CDKN2A/B, HHEX, TCF7L2 and KCNQ1 (8.5×10(-18)<P<8.5×10(-3)), as well as nominal associations of NOTCH2, JAZF1, KCNJ11 and HNF1B (0.05<P<0.1) with T2D risk, which yielded odds ratios ranging from 1.07 to 2.09. The 8 significant SNPs exhibited joint effect on increasing T2D risk, fasting plasma glucose and use of insulin therapy as well as reducing HOMA-β, BMI, waist circumference and younger age of diagnosis of T2D. The addition of CGS marginally increased AUC (2%) but significantly improved the predictive ability on T2D risk by 11.2% and 11.3% for unweighted and weighted CGS, respectively using the NRI approach (P<0.001).<h4>Conclusion</h4>In a Chinese population, the use of a CGS of 8 SNPs modestly but significantly improved its discriminative ability to predict T2D above and beyond that attributed to clinical risk factors (sex, age and BMI).
format	article
author	Claudia H T Tam Janice S K Ho Ying Wang Vincent K L Lam Heung Man Lee Guozhi Jiang Eric S H Lau Alice P S Kong Xiaodan Fan Jean L F Woo Stephen K W Tsui Maggie C Y Ng Wing Yee So Juliana C N Chan Ronald C W Ma
author_facet	Claudia H T Tam Janice S K Ho Ying Wang Vincent K L Lam Heung Man Lee Guozhi Jiang Eric S H Lau Alice P S Kong Xiaodan Fan Jean L F Woo Stephen K W Tsui Maggie C Y Ng Wing Yee So Juliana C N Chan Ronald C W Ma
author_sort	Claudia H T Tam
title	Use of net reclassification improvement (NRI) method confirms the utility of combined genetic risk score to predict type 2 diabetes.
title_short	Use of net reclassification improvement (NRI) method confirms the utility of combined genetic risk score to predict type 2 diabetes.
title_full	Use of net reclassification improvement (NRI) method confirms the utility of combined genetic risk score to predict type 2 diabetes.
title_fullStr	Use of net reclassification improvement (NRI) method confirms the utility of combined genetic risk score to predict type 2 diabetes.
title_full_unstemmed	Use of net reclassification improvement (NRI) method confirms the utility of combined genetic risk score to predict type 2 diabetes.
title_sort	use of net reclassification improvement (nri) method confirms the utility of combined genetic risk score to predict type 2 diabetes.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/45e049b9d1db45278d2b5c787b41bf48
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Use of net reclassification improvement (NRI) method confirms the utility of combined genetic risk score to predict type 2 diabetes.

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