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Comparison of the loci associated with HbA1c and blood glucose levels identified by a genome-wide association study in the Japanese population

発表形態:
原著論文
主要業績:
主要業績
単著・共著:
共著
発表年月:
2023年01月
DOI:
10.1007/s13340-023-00618-0
会議属性:
指定なし
査読:
有り
リンク情報:

日本語フィールド

著者:
*Sakashita T, Nakamura Y, Sutoh Y, Shimizu A, Hachiya T, Otsuka-Yamasaki Y, Takashima N, Kadota A, Miura K, Kita Y, Ikezaki H, Otonari J, Tanaka K, Shimanoe C, Koyama T, Watanabe I, Suzuki S, Nakagawa-Senda H, Hishida A, Tamura T, Kato Y, Okada R, Kuriki K, Katsuura-Kamano S, Watanabe T, Tanoue S, Koriyama C, Oze I, Koyanagi YN, Nakamura Y, Kusakabe M, Nakatochi M, Momozawa Y, Wakai K, Matsuo K
題名:
Comparison of the loci associated with HbA1c and blood glucose levels identified by a genome-wide association study in the Japanese population
発表情報:
Diabetol Int 巻: 14 号: 2 ページ: 188 - 198
キーワード:
Blood glucose; Body mass index; Diabetes; Genome-wide association study; HbA1c; Japanese population
概要:
Aims: Hemoglobin A1c (HbA1c) levels are widely employed to diagnose diabetes. However, estimates of the heritability of HbA1c and glucose levels are different. Therefore, we explored HbA1c- and blood glucose-associated loci in a non-diabetic Japanese population. Methods: We conducted a two-stage genome-wide association study (GWAS) on variants associated with HbA1c and blood glucose levels in a Japanese population. In the initial stage, data of 4911 participants of the Japan Multi-Institutional Collaborative Cohort (J-MICC) were subjected to discovery analysis. In the second stage, two datasets from the Tohoku Medical Megabank project, with 8175 and 40,519 participants, were used for the replication study. Association of the imputed variants with HbA1c and blood glucose levels was determined via linear regression analyses adjusted for age, sex, body mass index (BMI), smoking, and genetic principal components (PC1–PC10). Moreover, we performed a BMI-stratified GWAS on HbA1c levels in the J-MICC. The discovery analysis and BMI-stratified GWAS results were validated with re-analyses of normalized HbA1c levels adjusted for site in addition to the above, and blood glucose adjusted for fasting time as an additional covariate. Results: Genetic variants associated with HbA1c levels were identified in KCNQ1 and TMC6. None of the genetic variants associated with blood glucose levels in the discovery analysis were replicated. Association of rs2299620 in KCNQ1 with HbA1c levels showed heterogeneity between individuals with BMI ≥ 25 kg/m2 and BMI < 25 kg/m2. Conclusions: The variant rs2299620 in KCNQ1 might affect HbA1c levels differentially based on BMI grouping in the Japanese population.
抄録:

英語フィールド

Author:
*Sakashita T, Nakamura Y, Sutoh Y, Shimizu A, Hachiya T, Otsuka-Yamasaki Y, Takashima N, Kadota A, Miura K, Kita Y, Ikezaki H, Otonari J, Tanaka K, Shimanoe C, Koyama T, Watanabe I, Suzuki S, Nakagawa-Senda H, Hishida A, Tamura T, Kato Y, Okada R, Kuriki K, Katsuura-Kamano S, Watanabe T, Tanoue S, Koriyama C, Oze I, Koyanagi YN, Nakamura Y, Kusakabe M, Nakatochi M, Momozawa Y, Wakai K, Matsuo K
Title:
Comparison of the loci associated with HbA1c and blood glucose levels identified by a genome-wide association study in the Japanese population
Announcement information:
Diabetol Int Vol: 14 Issue: 2 Page: 188 - 198
Keyword:
Blood glucose; Body mass index; Diabetes; Genome-wide association study; HbA1c; Japanese population
An abstract:
Aims: Hemoglobin A1c (HbA1c) levels are widely employed to diagnose diabetes. However, estimates of the heritability of HbA1c and glucose levels are different. Therefore, we explored HbA1c- and blood glucose-associated loci in a non-diabetic Japanese population. Methods: We conducted a two-stage genome-wide association study (GWAS) on variants associated with HbA1c and blood glucose levels in a Japanese population. In the initial stage, data of 4911 participants of the Japan Multi-Institutional Collaborative Cohort (J-MICC) were subjected to discovery analysis. In the second stage, two datasets from the Tohoku Medical Megabank project, with 8175 and 40,519 participants, were used for the replication study. Association of the imputed variants with HbA1c and blood glucose levels was determined via linear regression analyses adjusted for age, sex, body mass index (BMI), smoking, and genetic principal components (PC1–PC10). Moreover, we performed a BMI-stratified GWAS on HbA1c levels in the J-MICC. The discovery analysis and BMI-stratified GWAS results were validated with re-analyses of normalized HbA1c levels adjusted for site in addition to the above, and blood glucose adjusted for fasting time as an additional covariate. Results: Genetic variants associated with HbA1c levels were identified in KCNQ1 and TMC6. None of the genetic variants associated with blood glucose levels in the discovery analysis were replicated. Association of rs2299620 in KCNQ1 with HbA1c levels showed heterogeneity between individuals with BMI ≥ 25 kg/m2 and BMI < 25 kg/m2. Conclusions: The variant rs2299620 in KCNQ1 might affect HbA1c levels differentially based on BMI grouping in the Japanese population.


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