Evaluating the discriminative power of multi-trait genetic risk scores for type 2 diabetes in a northern Swedish population
(2010) In Diabetologia 53(10). p.2155-2162- Abstract
- We determined whether single nucleotide polymorphisms (SNPs) previously associated with diabetogenic traits improve the discriminative power of a type 2 diabetes genetic risk score. Participants (n = 2,751) were genotyped for 73 SNPs previously associated with type 2 diabetes, fasting glucose/insulin concentrations, obesity or lipid levels, from which five genetic risk scores (one for each of the four traits and one combining all SNPs) were computed. Type 2 diabetes patients and non-diabetic controls (n = 1,327/1,424) were identified using medical records in addition to an independent oral glucose tolerance test. Model 1, including only SNPs associated with type 2 diabetes, had a discriminative power of 0.591 (p < 1.00 x 10(-20) vs null... (More)
- We determined whether single nucleotide polymorphisms (SNPs) previously associated with diabetogenic traits improve the discriminative power of a type 2 diabetes genetic risk score. Participants (n = 2,751) were genotyped for 73 SNPs previously associated with type 2 diabetes, fasting glucose/insulin concentrations, obesity or lipid levels, from which five genetic risk scores (one for each of the four traits and one combining all SNPs) were computed. Type 2 diabetes patients and non-diabetic controls (n = 1,327/1,424) were identified using medical records in addition to an independent oral glucose tolerance test. Model 1, including only SNPs associated with type 2 diabetes, had a discriminative power of 0.591 (p < 1.00 x 10(-20) vs null model) as estimated by the area under the receiver operator characteristic curve (ROC AUC). Model 2, including only fasting glucose/insulin SNPs, had a significantly higher discriminative power than the null model (ROC AUC 0.543; p = 9.38 x 10(-6) vs null model), but lower discriminative power than model 1 (p = 5.92 x 10(-5)). Model 3, with only lipid-associated SNPs, had significantly higher discriminative power than the null model (ROC AUC 0.565; p = 1.44 x 10(-9)) and was not statistically different from model 1 (p = 0.083). The ROC AUC of model 4, which included only obesity SNPs, was 0.557 (p = 2.30 x 10(-7) vs null model) and smaller than model 1 (p = 0.025). Finally, the model including all SNPs yielded a significant improvement in discriminative power compared with the null model (p < 1.0 x 10(-20)) and model 1 (p = 1.32 x 10(-5)); its ROC AUC was 0.626. Adding SNPs previously associated with fasting glucose, insulin, lipids or obesity to a genetic risk score for type 2 diabetes significantly increases the power to discriminate between people with and without clinically manifest type 2 diabetes compared with a model including only conventional type 2 diabetes loci. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1697790
- author
- Fontaine-Bisson, B. ; Renstrom, F. ; Rolandsson, O. ; Payne, F. ; Hallmans, G. ; Barroso, I. and Franks, Paul LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Type 2 diabetes, Predictive power, Polymorphism, Obesity, Lipids, Insulin, Glucose, Discriminative power, Genetic risk score
- in
- Diabetologia
- volume
- 53
- issue
- 10
- pages
- 2155 - 2162
- publisher
- Springer
- external identifiers
-
- wos:000281612600012
- scopus:77958027965
- pmid:20571754
- ISSN
- 1432-0428
- DOI
- 10.1007/s00125-010-1792-y
- language
- English
- LU publication?
- yes
- id
- dbb69f85-5914-4c32-9f3e-a08dc6764582 (old id 1697790)
- date added to LUP
- 2016-04-01 10:07:51
- date last changed
- 2024-02-21 08:51:18
@article{dbb69f85-5914-4c32-9f3e-a08dc6764582,
abstract = {{We determined whether single nucleotide polymorphisms (SNPs) previously associated with diabetogenic traits improve the discriminative power of a type 2 diabetes genetic risk score. Participants (n = 2,751) were genotyped for 73 SNPs previously associated with type 2 diabetes, fasting glucose/insulin concentrations, obesity or lipid levels, from which five genetic risk scores (one for each of the four traits and one combining all SNPs) were computed. Type 2 diabetes patients and non-diabetic controls (n = 1,327/1,424) were identified using medical records in addition to an independent oral glucose tolerance test. Model 1, including only SNPs associated with type 2 diabetes, had a discriminative power of 0.591 (p < 1.00 x 10(-20) vs null model) as estimated by the area under the receiver operator characteristic curve (ROC AUC). Model 2, including only fasting glucose/insulin SNPs, had a significantly higher discriminative power than the null model (ROC AUC 0.543; p = 9.38 x 10(-6) vs null model), but lower discriminative power than model 1 (p = 5.92 x 10(-5)). Model 3, with only lipid-associated SNPs, had significantly higher discriminative power than the null model (ROC AUC 0.565; p = 1.44 x 10(-9)) and was not statistically different from model 1 (p = 0.083). The ROC AUC of model 4, which included only obesity SNPs, was 0.557 (p = 2.30 x 10(-7) vs null model) and smaller than model 1 (p = 0.025). Finally, the model including all SNPs yielded a significant improvement in discriminative power compared with the null model (p < 1.0 x 10(-20)) and model 1 (p = 1.32 x 10(-5)); its ROC AUC was 0.626. Adding SNPs previously associated with fasting glucose, insulin, lipids or obesity to a genetic risk score for type 2 diabetes significantly increases the power to discriminate between people with and without clinically manifest type 2 diabetes compared with a model including only conventional type 2 diabetes loci.}},
author = {{Fontaine-Bisson, B. and Renstrom, F. and Rolandsson, O. and Payne, F. and Hallmans, G. and Barroso, I. and Franks, Paul}},
issn = {{1432-0428}},
keywords = {{Type 2 diabetes; Predictive power; Polymorphism; Obesity; Lipids; Insulin; Glucose; Discriminative power; Genetic risk score}},
language = {{eng}},
number = {{10}},
pages = {{2155--2162}},
publisher = {{Springer}},
series = {{Diabetologia}},
title = {{Evaluating the discriminative power of multi-trait genetic risk scores for type 2 diabetes in a northern Swedish population}},
url = {{http://dx.doi.org/10.1007/s00125-010-1792-y}},
doi = {{10.1007/s00125-010-1792-y}},
volume = {{53}},
year = {{2010}},
}