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

被引：0

作者：

Sakashita, Takuya ^{[1
,2
]}

Nakamura, Yasuyuki ^{[1
,3
]}

Sutoh, Yoichi ^{[4
]}

Shimizu, Atsushi ^{[4
]}

Hachiya, Tsuyoshi ^{[4
]}

Otsuka-Yamasaki, Yayoi ^{[4
]}

Takashima, Naoyuki ^{[1
,5
,13
]}

Kadota, Aya ^{[1
,6
]}

Miura, Katsuyuki ^{[1
,6
]}

Kita, Yoshikuni ^{[1
,7
]}

Ikezaki, Hiroaki ^{[8
,9
]}

Otonari, Jun ^{[10
]}

Tanaka, Keitaro ^{[11
]}

Shimanoe, Chisato ^{[12
]}

Koyama, Teruhide ^{[13
]}

Watanabe, Isao ^{[13
]}

Suzuki, Sadao ^{[14
]}

Nakagawa-Senda, Hiroko ^{[14
]}

Hishida, Asahi ^{[15
]}

Tamura, Takashi ^{[15
]}

Kato, Yasufumi ^{[15
]}

Okada, Rieko ^{[15
]}

Kuriki, Kiyonori ^{[16
]}

Katsuura-Kamano, Sakurako ^{[17
]}

Watanabe, Takeshi ^{[17
]}

Tanoue, Shiroh ^{[18
]}

Koriyama, Chihaya ^{[18
]}

Oze, Isao ^{[19
]}

Koyanagi, Yuriko N. ^{[20
]}

Nakamura, Yohko ^{[21
]}

Kusakabe, Miho ^{[21
]}

Nakatochi, Masahiro ^{[22
]}

Momozawa, Yukihide ^{[23
]}

Wakai, Kenji ^{[15
]}

Matsuo, Keitaro ^{[19
,24
]}

机构：

[1] Shiga Univ Med Sci, Dept Publ Hlth, Seta Tsukinowa Cho, Otsu, Shiga 5202192, Japan

[2] TAKARA BIO INC, 7-4-38 Nojihigashi, Kusatsu, Shiga 5250058, Japan

[3] Takeda Hosp, Med Examinat Ctr, Kyoto, Japan

[4] Iwate Med Univ, Iwate Tohoku Med Megabank Org, Div Biomed Informat Anal, 1-1-1 Idaidori, Yahaba, Iwate 0283694, Japan

[5] Kindai Univ, Fac Med, Dept Publ Hlth, 377-2 Ohnohigashi, Osaka 5898511, Japan

[6] Shiga Univ Med Sci, NCD Epidemiol Res Ctr, Seta Tsukinowa Cho, Otsu, Shiga 5202192, Japan

[7] Tsuruga Nursing Univ, Fac Nursing Sci, 78-2-1 Kizaki, Tsuruga, Fukui 9140814, Japan

[8] Kyushu Univ, Fac Med Sci, Dept Comprehens Gen Internal Med, 3-1-1 Maidashi,Higashi Ku, Fukuoka 8128582, Japan

[9] Kyushu Univ Hosp, Dept Gen Internal Med, 3-1-1 Maidashi,Higashi Ku, Fukuoka 8128582, Japan

[10] Kyushu Univ, Grad Sch Med Sci, Dept Psychosomat Med, 3-1-1 Maidashi,Higashi Ku, Fukuoka 8128582, Japan

[11] Saga Univ, Fac Med, Dept Prevent Med, 5-1-1 Nabeshima, Saga 8498501, Japan

[12] Saga Univ Hosp, Dept Pharm, 5-1-1 Nabeshima, Saga 8498501, Japan

[13] Kyoto Prefectural Univ Med, Dept Epidemiol Community Hlth & Med, 465 Kajii Cho, Kamigyo Ku, Kyoto 6028566, Japan

[14] Nagoya City Univ, Dept Publ Hlth, Grad Sch Med Sci, 1 Kawasumi,Mizuho Cho, Mizuho Ku, Nagoya 4678601, Japan

[15] Nagoya Univ, Dept Prevent Med, Grad Sch Med, 65 Tsurumai Cho,Showa Ku, Nagoya 4668550, Japan

[16] Univ Shizuoka, Sch Food & Nutr Sci, Div Nutr Sci, Lab Publ Hlth, 52-1 Yada,Suruga Ku, Shizuoka 4228526, Japan

[17] Tokushima Univ, Dept Prevent Med, Grad Sch Biomed Sci, 3-18-15 Kuramoto Cho, Tokushima 7708503, Japan

[18] Kagoshima Univ, Dept Epidemiol & Prevent Med, Grad Sch Med & Dent Sci, 8-35-1 Sakuragaoka, Kagoshima 8908544, Japan

[19] Aichi Canc Ctr Res Inst, Div Canc Epidemiol & Prevent, 1-1 Kanokoden,Chikusa Ku, Nagoya 4648681, Japan

[20] Aichi Canc Ctr, Res Inst, Div Canc Informat & Control, 1-1 Kanokoden,Chikusa Ku, Nagoya 4648681, Japan

[21] Chiba Canc Ctr, Res Inst, Canc Prevent Ctr, 666-2 Nitona-cho,Chuo Ku, Chiba 2608717, Japan

[22] Nagoya Univ, Dept Integrated Hlth Sci, Publ Hlth Informat Unit, Grad Sch Med, 1-1-20 Daiko Minami,Higashi Ku, Nagoya 4618673, Japan

[23] RIKEN, Ctr Integrat Med Sci, Lab Genotyping Dev, 1-7-22 Suehiro Cho,Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

[24] Nagoya Univ, Div Canc Epidemiol, Grad Sch Med, 65 Tsurumai Cho, Showa Ku, Nagoya 4668550, Japan

来源：

DIABETOLOGY INTERNATIONAL | 2023年 / 14卷 / 02期

关键词：

Blood glucose; Body mass index; Diabetes; Genome-wide association study; HbA1c; Japanese population; GENOTYPE IMPUTATION; GLYCATED HEMOGLOBIN; GENE; VARIANTS; KCNQ1; VISUALIZATION; TRAITS;

D O I：

10.1007/s13340-023-00618-0

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

AimsHemoglobin 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.MethodsWe 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.ResultsGenetic 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/m(2) and BMI < 25 kg/m(2).ConclusionsThe variant rs2299620 in KCNQ1 might affect HbA1c levels differentially based on BMI grouping in the Japanese population.

引用

页码：188 / 198

页数：11

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