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A genetic risk score that includes common type 2 diabetes risk variants is associated with gestational diabetes
Author(s) -
Kawai V. K.,
Levinson R. T.,
Adefurin A.,
Kurnik D.,
Collier S. P.,
Conway D.,
Stein C. M.
Publication year - 2017
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.13356
Subject(s) - gestational diabetes , medicine , odds ratio , body mass index , type 2 diabetes , diabetes mellitus , pregnancy , obstetrics , population , case control study , area under the curve , endocrinology , gynecology , gestation , biology , genetics , environmental health
Summary Objective Gestational diabetes ( GDM ) is characterized by maternal glucose intolerance that manifests during pregnancy. Because GDM resembles type 2 diabetes (T2 DM ), shared genetic predisposition is likely but has not been established. We tested the hypothesis that a genetic risk score ( GRS ) that included variants known to be associated with T2 DM is associated with GDM . Study design We conducted a case‐control study using the Vanderbilt Medical Center biobank (Bio VU ) and calculated a simple‐count GRS using 34 variants previously associated with T2 DM or fasting glucose in the general population, or with GDM or glucose intolerance in pregnancy. We assessed the association of the GRS with GDM adjusting for maternal age, parity, and body mass index ( BMI ) and calculated the area under the curve for the receiver‐operating characteristic curve (c‐statistic). Study population Among Caucasian women, we identified 458 cases of GDM and 1538 pregnant controls with normal glucose tolerance. Results Cases of GDM had a higher number of risk alleles compared to controls (38.9±4.0 vs 37.4±4.0 risk alleles, P=1.6×10 −11 ). The GRS was significantly associated with GDM ; the adjusted odds ratio associated with each additional risk allele was 1.10 (95% CI : 1.07‐1.13, P=6×10 −11 ). Clinical variables predicted the risk of GDM (c‐statistic 0.67, 95% CI : 0.64‐0.70), and adding the GRS modestly improved prediction (0.70, 95% CI : 0.67‐0.73). Conclusions Among Caucasian women, a GRS that included common T2 DM genetic risk variants was associated with increased risk of GDM but showed limited utility in the identification of GDM cases.