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

IF 1.3 Q4 ENDOCRINOLOGY & METABOLISM

Diabetology International Pub Date : 2023-01-27 eCollection Date: 2023-04-01 DOI:10.1007/s13340-023-00618-0

Takuya Sakashita, Yasuyuki Nakamura, Yoichi Sutoh, Atsushi Shimizu, Tsuyoshi Hachiya, Yayoi Otsuka-Yamasaki, Naoyuki Takashima, Aya Kadota, Katsuyuki Miura, Yoshikuni Kita, Hiroaki Ikezaki, Jun Otonari, Keitaro Tanaka, Chisato Shimanoe, Teruhide Koyama, Isao Watanabe, Sadao Suzuki, Hiroko Nakagawa-Senda, Asahi Hishida, Takashi Tamura, Yasufumi Kato, Rieko Okada, Kiyonori Kuriki, Sakurako Katsuura-Kamano, Takeshi Watanabe, Shiroh Tanoue, Chihaya Koriyama, Isao Oze, Yuriko N Koyanagi, Yohko Nakamura, Miho Kusakabe, Masahiro Nakatochi, Yukihide Momozawa, Kenji Wakai, Keitaro Matsuo

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引用次数: 0

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.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-023-00618-0.

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比较日本人群中通过全基因组关联研究发现的与 HbA1c 和血糖水平相关的基因位点。

目的：血红蛋白 A1c（HbA1c）水平被广泛用于诊断糖尿病。然而，对 HbA1c 和血糖水平遗传性的估计却不尽相同。因此，我们在非糖尿病日本人群中探索了与 HbA1c 和血糖相关的基因位点：我们对日本人群中与 HbA1c 和血糖水平相关的变异进行了两阶段全基因组关联研究（GWAS）。在第一阶段，我们对日本多机构协作队列（J-MICC）中 4911 名参与者的数据进行了发现分析。第二阶段的复制研究使用了来自东北医学巨型数据库项目的两个数据集，分别有 8175 名和 40519 名参与者。通过调整年龄、性别、体重指数（BMI）、吸烟和遗传主成分（PC1-PC10）的线性回归分析，确定了估算变异与 HbA1c 和血糖水平的关系。此外，我们还对 J-MICC 中的 HbA1c 水平进行了 BMI 分层 GWAS 分析。发现分析和 BMI 分层 GWAS 结果通过对归一化 HbA1c 水平的重新分析进行了验证，除上述分析外，还根据地点进行了调整，并将空腹时间作为额外的协变量对血糖进行了调整：结果：在 KCNQ1 和 TMC6 中发现了与 HbA1c 水平相关的基因变异。在发现分析中，与血糖水平相关的基因变异均未被复制。KCNQ1 中的 rs2299620 与 HbA1c 水平的关系在体重指数≥ 25 kg/m2 和体重指数为 2 的个体之间表现出异质性：结论：在日本人群中，KCNQ1中的变异体rs2299620可能会根据BMI分组对HbA1c水平产生不同的影响：在线版本包含补充材料，可在 10.1007/s13340-023-00618-0。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetology International ENDOCRINOLOGY & METABOLISM-

CiteScore

3.90

自引率

4.50%

发文量

期刊介绍： Diabetology International, the official journal of the Japan Diabetes Society, publishes original research articles about experimental research and clinical studies in diabetes and related areas. The journal also presents editorials, reviews, commentaries, reports of expert committees, and case reports on any aspect of diabetes. Diabetology International welcomes submissions from researchers, clinicians, and health professionals throughout the world who are interested in research, treatment, and care of patients with diabetes. All manuscripts are peer-reviewed to assure that high-quality information in the field of diabetes is made available to readers. Manuscripts are reviewed with due respect for the author''s confidentiality. At the same time, reviewers also have rights to confidentiality, which are respected by the editors. The journal follows a single-blind review procedure, where the reviewers are aware of the names and affiliations of the authors, but the reviewer reports provided to authors are anonymous. Single-blind peer review is the traditional model of peer review that many reviewers are comfortable with, and it facilitates a dispassionate critique of a manuscript.