Assessing the clinical utility of a genetic risk score constructed using 49 susceptibility alleles for type 2 diabetes in a Japanese population

Minako Imamura, Daichi Shigemizu, Tatsuhiko Tsunoda, Minoru Iwata, Hiroshi Maegawa, Hirotaka Watada, Hiroshi Hirose, Yasushi Tanaka, Kazuyuki Tobe, Kohei Kaku, Atsunori Kashiwagi, Ryuzo Kawamori, Shiro Maeda

Research output: Contribution to journalArticle

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Abstract

Context: Genome-wide association studies (GWASs) have identified over 60 susceptibility loci for type 2 diabetes (T2D). Although the ability of previous genetic information (∼40 loci) to discriminate between susceptible and nonsusceptible individuals is limited, the added benefit of updated genetic information has not been evaluated. Objective: We assessed the clinical utility of GWAS-derived T2D susceptibility variants in a Japanese population. Design and Setting: We conducted a cross-sectional case-control study. Participants: T2D cases (n = 2613) and controls (n = 1786) with complete genotype data for 49 single-nucleotide polymorphisms (SNPs) were selected for analyses. Outcome Measures: We constructed genetic risk scores (GRSs) by summing the susceptibility alleles of 49 SNP loci for T2D (GRS-49) or 10 SNP loci with genome-wide significant association in previous Japanese studies (GRS-10) and examined the association of the GRSs with the disease by receiver operating characteristic analyses using a logistic regression model. Results: The GRS-49 was significantly associated with T2D (P = 8.75 × 10-45). The area under the curve (AUC) for GRS-49 alone (model 1) and forage, sex, and body mass index (model 2) was 0.624 and 0.743, respectively. Addition of the GRS-49 to model 2 resulted in a small but significant increase in the AUC (AAUC = 0.03, P = 7.99 × 10-15). Receiver operating characteristic AUC was greater for GRS-49 than for GRS-10 (0.624 vs 0.603, P =.019), whereas the odds ratio per risk allele was smaller for GRS-49 than for GRS-10 (GRS-49, 1.13, 95% confidence interval 1.11-1.15; GRS-10, 1.26, 95% confidence interval = 1.22-1.31, P = 7.31 × 10-10). The GRS-49 was significantly associated with age at diagnosis in 1591 cases (β = -0.199, P =.0069) and with fasting plasma glucose in 804 controls (β = 0.009, P = 0.021). Conclusions: Updated genetic information slightly improves disease prediction ability but is not sufficiently robust for translation into clinical practice.

Original languageEnglish
JournalJournal of Clinical Endocrinology and Metabolism
Volume98
Issue number10
DOIs
Publication statusPublished - 2013 Oct

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Medical problems
Type 2 Diabetes Mellitus
Alleles
Population
Polymorphism
Area Under Curve
Single Nucleotide Polymorphism
Nucleotides
Genes
Genome-Wide Association Study
ROC Curve
Logistic Models
Confidence Intervals
Aptitude
Logistics
Case-Control Studies
Fasting
Body Mass Index

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

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Assessing the clinical utility of a genetic risk score constructed using 49 susceptibility alleles for type 2 diabetes in a Japanese population. / Imamura, Minako; Shigemizu, Daichi; Tsunoda, Tatsuhiko; Iwata, Minoru; Maegawa, Hiroshi; Watada, Hirotaka; Hirose, Hiroshi; Tanaka, Yasushi; Tobe, Kazuyuki; Kaku, Kohei; Kashiwagi, Atsunori; Kawamori, Ryuzo; Maeda, Shiro.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 98, No. 10, 10.2013.

Research output: Contribution to journalArticle

Imamura, M, Shigemizu, D, Tsunoda, T, Iwata, M, Maegawa, H, Watada, H, Hirose, H, Tanaka, Y, Tobe, K, Kaku, K, Kashiwagi, A, Kawamori, R & Maeda, S 2013, 'Assessing the clinical utility of a genetic risk score constructed using 49 susceptibility alleles for type 2 diabetes in a Japanese population', Journal of Clinical Endocrinology and Metabolism, vol. 98, no. 10. https://doi.org/10.1210/jc.2013-1642
Imamura, Minako ; Shigemizu, Daichi ; Tsunoda, Tatsuhiko ; Iwata, Minoru ; Maegawa, Hiroshi ; Watada, Hirotaka ; Hirose, Hiroshi ; Tanaka, Yasushi ; Tobe, Kazuyuki ; Kaku, Kohei ; Kashiwagi, Atsunori ; Kawamori, Ryuzo ; Maeda, Shiro. / Assessing the clinical utility of a genetic risk score constructed using 49 susceptibility alleles for type 2 diabetes in a Japanese population. In: Journal of Clinical Endocrinology and Metabolism. 2013 ; Vol. 98, No. 10.
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abstract = "Context: Genome-wide association studies (GWASs) have identified over 60 susceptibility loci for type 2 diabetes (T2D). Although the ability of previous genetic information (∼40 loci) to discriminate between susceptible and nonsusceptible individuals is limited, the added benefit of updated genetic information has not been evaluated. Objective: We assessed the clinical utility of GWAS-derived T2D susceptibility variants in a Japanese population. Design and Setting: We conducted a cross-sectional case-control study. Participants: T2D cases (n = 2613) and controls (n = 1786) with complete genotype data for 49 single-nucleotide polymorphisms (SNPs) were selected for analyses. Outcome Measures: We constructed genetic risk scores (GRSs) by summing the susceptibility alleles of 49 SNP loci for T2D (GRS-49) or 10 SNP loci with genome-wide significant association in previous Japanese studies (GRS-10) and examined the association of the GRSs with the disease by receiver operating characteristic analyses using a logistic regression model. Results: The GRS-49 was significantly associated with T2D (P = 8.75 × 10-45). The area under the curve (AUC) for GRS-49 alone (model 1) and forage, sex, and body mass index (model 2) was 0.624 and 0.743, respectively. Addition of the GRS-49 to model 2 resulted in a small but significant increase in the AUC (AAUC = 0.03, P = 7.99 × 10-15). Receiver operating characteristic AUC was greater for GRS-49 than for GRS-10 (0.624 vs 0.603, P =.019), whereas the odds ratio per risk allele was smaller for GRS-49 than for GRS-10 (GRS-49, 1.13, 95{\%} confidence interval 1.11-1.15; GRS-10, 1.26, 95{\%} confidence interval = 1.22-1.31, P = 7.31 × 10-10). The GRS-49 was significantly associated with age at diagnosis in 1591 cases (β = -0.199, P =.0069) and with fasting plasma glucose in 804 controls (β = 0.009, P = 0.021). Conclusions: Updated genetic information slightly improves disease prediction ability but is not sufficiently robust for translation into clinical practice.",
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T1 - Assessing the clinical utility of a genetic risk score constructed using 49 susceptibility alleles for type 2 diabetes in a Japanese population

AU - Imamura, Minako

AU - Shigemizu, Daichi

AU - Tsunoda, Tatsuhiko

AU - Iwata, Minoru

AU - Maegawa, Hiroshi

AU - Watada, Hirotaka

AU - Hirose, Hiroshi

AU - Tanaka, Yasushi

AU - Tobe, Kazuyuki

AU - Kaku, Kohei

AU - Kashiwagi, Atsunori

AU - Kawamori, Ryuzo

AU - Maeda, Shiro

PY - 2013/10

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N2 - Context: Genome-wide association studies (GWASs) have identified over 60 susceptibility loci for type 2 diabetes (T2D). Although the ability of previous genetic information (∼40 loci) to discriminate between susceptible and nonsusceptible individuals is limited, the added benefit of updated genetic information has not been evaluated. Objective: We assessed the clinical utility of GWAS-derived T2D susceptibility variants in a Japanese population. Design and Setting: We conducted a cross-sectional case-control study. Participants: T2D cases (n = 2613) and controls (n = 1786) with complete genotype data for 49 single-nucleotide polymorphisms (SNPs) were selected for analyses. Outcome Measures: We constructed genetic risk scores (GRSs) by summing the susceptibility alleles of 49 SNP loci for T2D (GRS-49) or 10 SNP loci with genome-wide significant association in previous Japanese studies (GRS-10) and examined the association of the GRSs with the disease by receiver operating characteristic analyses using a logistic regression model. Results: The GRS-49 was significantly associated with T2D (P = 8.75 × 10-45). The area under the curve (AUC) for GRS-49 alone (model 1) and forage, sex, and body mass index (model 2) was 0.624 and 0.743, respectively. Addition of the GRS-49 to model 2 resulted in a small but significant increase in the AUC (AAUC = 0.03, P = 7.99 × 10-15). Receiver operating characteristic AUC was greater for GRS-49 than for GRS-10 (0.624 vs 0.603, P =.019), whereas the odds ratio per risk allele was smaller for GRS-49 than for GRS-10 (GRS-49, 1.13, 95% confidence interval 1.11-1.15; GRS-10, 1.26, 95% confidence interval = 1.22-1.31, P = 7.31 × 10-10). The GRS-49 was significantly associated with age at diagnosis in 1591 cases (β = -0.199, P =.0069) and with fasting plasma glucose in 804 controls (β = 0.009, P = 0.021). Conclusions: Updated genetic information slightly improves disease prediction ability but is not sufficiently robust for translation into clinical practice.

AB - Context: Genome-wide association studies (GWASs) have identified over 60 susceptibility loci for type 2 diabetes (T2D). Although the ability of previous genetic information (∼40 loci) to discriminate between susceptible and nonsusceptible individuals is limited, the added benefit of updated genetic information has not been evaluated. Objective: We assessed the clinical utility of GWAS-derived T2D susceptibility variants in a Japanese population. Design and Setting: We conducted a cross-sectional case-control study. Participants: T2D cases (n = 2613) and controls (n = 1786) with complete genotype data for 49 single-nucleotide polymorphisms (SNPs) were selected for analyses. Outcome Measures: We constructed genetic risk scores (GRSs) by summing the susceptibility alleles of 49 SNP loci for T2D (GRS-49) or 10 SNP loci with genome-wide significant association in previous Japanese studies (GRS-10) and examined the association of the GRSs with the disease by receiver operating characteristic analyses using a logistic regression model. Results: The GRS-49 was significantly associated with T2D (P = 8.75 × 10-45). The area under the curve (AUC) for GRS-49 alone (model 1) and forage, sex, and body mass index (model 2) was 0.624 and 0.743, respectively. Addition of the GRS-49 to model 2 resulted in a small but significant increase in the AUC (AAUC = 0.03, P = 7.99 × 10-15). Receiver operating characteristic AUC was greater for GRS-49 than for GRS-10 (0.624 vs 0.603, P =.019), whereas the odds ratio per risk allele was smaller for GRS-49 than for GRS-10 (GRS-49, 1.13, 95% confidence interval 1.11-1.15; GRS-10, 1.26, 95% confidence interval = 1.22-1.31, P = 7.31 × 10-10). The GRS-49 was significantly associated with age at diagnosis in 1591 cases (β = -0.199, P =.0069) and with fasting plasma glucose in 804 controls (β = 0.009, P = 0.021). Conclusions: Updated genetic information slightly improves disease prediction ability but is not sufficiently robust for translation into clinical practice.

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