在日本人群中通过全基因组关联研究确定的与糖化血红蛋白（HbA1c）和血糖水平相关的基因座比较。
Comparison of the loci associated with HbA1c and blood glucose levels identified by a genome-wide association study in the Japanese population.
作者信息
Sakashita Takuya, Nakamura Yasuyuki, Sutoh Yoichi, Shimizu Atsushi, Hachiya Tsuyoshi, Otsuka-Yamasaki Yayoi, Takashima Naoyuki, Kadota Aya, Miura Katsuyuki, Kita Yoshikuni, Ikezaki Hiroaki, Otonari Jun, Tanaka Keitaro, Shimanoe Chisato, Koyama Teruhide, Watanabe Isao, Suzuki Sadao, Nakagawa-Senda Hiroko, Hishida Asahi, Tamura Takashi, Kato Yasufumi, Okada Rieko, Kuriki Kiyonori, Katsuura-Kamano Sakurako, Watanabe Takeshi, Tanoue Shiroh, Koriyama Chihaya, Oze Isao, Koyanagi Yuriko N, Nakamura Yohko, Kusakabe Miho, Nakatochi Masahiro, Momozawa Yukihide, Wakai Kenji, Matsuo Keitaro
机构信息
Department of Public Health, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192 Japan.
TAKARA BIO INC., 7-4-38 Nojihigashi, Kusatsu, Shiga 525-0058 Japan.
出版信息
Diabetol Int. 2023 Jan 27;14(2):188-198. doi: 10.1007/s13340-023-00618-0. eCollection 2023 Apr.
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 and . None of the genetic variants associated with blood glucose levels in the discovery analysis were replicated. Association of rs2299620 in with HbA1c levels showed heterogeneity between individuals with BMI ≥ 25 kg/m and BMI < 25 kg/m.
CONCLUSIONS
The variant rs2299620 in 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.
目的
糖化血红蛋白（HbA1c）水平被广泛用于诊断糖尿病。然而，HbA1c和血糖水平的遗传力估计有所不同。因此，我们在非糖尿病日本人群中探索了与HbA1c和血糖相关的基因座。
方法
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）。在初始阶段，对日本多机构合作队列（J-MICC）的4911名参与者的数据进行发现分析。在第二阶段，来自东北医学大数据项目的两个数据集，分别有8175名和40519名参与者，用于重复研究。通过对年龄、性别、体重指数（BMI）、吸烟和遗传主成分（PC1-PC10）进行调整的线性回归分析，确定推断变异与HbA1c和血糖水平的关联。此外，我们在J-MICC中对HbA1c水平进行了BMI分层的GWAS。发现分析和BMI分层GWAS结果通过对上述因素以及根据位点调整的标准化HbA1c水平进行重新分析，以及将空腹时间作为额外协变量调整的血糖进行验证。
结果
在[具体位置1]和[具体位置2]中鉴定出与HbA1c水平相关的基因变异。发现分析中与血糖水平相关的基因变异均未得到重复验证。[具体位置3]中的rs2299620与HbA1c水平的关联在BMI≥25 kg/m²和BMI<25 kg/m²的个体之间表现出异质性。
结论
在日本人群中，[具体位置3]中的变异rs2299620可能根据BMI分组对HbA1c水平产生不同影响。
补充信息
在线版本包含可在10.1007/s13340-023-00618-0获取的补充材料。
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