Polygenic type 2 diabetes prediction at the limit of common variant detection

Genome-wide association studies (GWAS) may have reached their limit of detecting common type 2 diabetes (T2D)-associated genetic variation. We evaluated the performance of current polygenic T2D prediction. Using data from the Framingham Offspring (FOS) and the Coronary Artery Risk Development in You...

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Vydáno v:Diabetes (New York, N.Y.) Ročník 63; číslo 6; s. 2172
Hlavní autoři: Vassy, Jason L, Hivert, Marie-France, Porneala, Bianca, Dauriz, Marco, Florez, Jose C, Dupuis, Josée, Siscovick, David S, Fornage, Myriam, Rasmussen-Torvik, Laura J, Bouchard, Claude, Meigs, James B
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.06.2014
Témata:
Adolescent
Adult
Aged
Black or African American - genetics
Child
Child, Preschool
Diabetes Mellitus, Type 2 - epidemiology
Diabetes Mellitus, Type 2 - genetics
Environmental Exposure
Female
Follow-Up Studies
Genetic Predisposition to Disease
Genetic Variation
Genome-Wide Association Study
Genotype
Humans
Insulin Resistance - genetics
Male
Middle Aged
Obesity - complications
Obesity - genetics
Polymorphism, Single Nucleotide
Proportional Hazards Models
Prospective Studies
Risk Factors
Sedentary Behavior
White People - genetics
ISSN:1939-327X, 1939-327X
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Shrnutí:Genome-wide association studies (GWAS) may have reached their limit of detecting common type 2 diabetes (T2D)-associated genetic variation. We evaluated the performance of current polygenic T2D prediction. Using data from the Framingham Offspring (FOS) and the Coronary Artery Risk Development in Young Adults (CARDIA) studies, we tested three hypotheses: 1) a 62-locus genotype risk score (GRSt) improves T2D prediction compared with previous less inclusive GRSt; 2) separate GRS for β-cell (GRSβ) and insulin resistance (GRSIR) independently predict T2D; and 3) the relationships between T2D and GRSt, GRSβ, or GRSIR do not differ between blacks and whites. Among 1,650 young white adults in CARDIA, 820 young black adults in CARDIA, and 3,471 white middle-aged adults in FOS, cumulative T2D incidence was 5.9%, 14.4%, and 12.9%, respectively, over 25 years. The 62-locus GRSt was significantly associated with incident T2D in all three groups. In FOS but not CARDIA, the 62-locus GRSt improved the model C statistic (0.698 and 0.726 for models without and with GRSt, respectively; P < 0.001) but did not materially improve risk reclassification in either study. Results were similar among blacks compared with whites. The GRSβ but not GRSIR predicted incident T2D among FOS and CARDIA whites. At the end of the era of common variant discovery for T2D, polygenic scores can predict T2D in whites and blacks but do not outperform clinical models. Further optimization of polygenic prediction may require novel analytic methods, including less common as well as functional variants.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1939-327X
1939-327X
DOI:10.2337/db13-1663