Multiple Nonglycemic Genomic Loci Are Newly Associated With Blood Level of Glycated Hemoglobin in East Asians

被引：55

作者：

Chen, Peng ^{[1
,2
]}

Takeuchi, Fumihiko ^{[3
]}

Lee, Jong-Young ^{[4
]}

Li, Huaixing ^{[5
]}

Wu, Jer-Yuarn ^{[6
,7
]}

Liang, Jun ^{[8
]}

Long, Jirong ^{[9
,10
]}

Tabara, Yasuharu ^{[11
]}

Goodarzi, Mark O. ^{[12
]}

Pereira, Mark A. ^{[13
]}

Kim, Young Jin ^{[4
]}

Go, Min Jin ^{[4
]}

Stram, Daniel O. ^{[14
]}

Vithana, Eranga ^{[15
,16
,17
]}

Khor, Chiea-Chuen ^{[1
,2
,16
,18
,19
]}

Liu, Jianjun ^{[1
,2
,18
]}

Liao, Jiemin ^{[15
,16
]}

Ye, Xingwang ^{[5
]}

Wang, Yiqin ^{[5
]}

Lu, Ling ^{[5
]}

Young, Terri L. ^{[17
,20
]}

Lee, Jeannette ^{[1
,2
]}

Thai, Ah Chuan ^{[21
]}

Cheng, Ching-Yu ^{[1
,2
,15
,16
,22
]}

van Dam, Rob M. ^{[1
,2
,21
]}

Friedlander, Yechiel ^{[23
]}

Heng, Chew-Kiat ^{[19
]}

Koh, Woon-Puay ^{[1
,2
,24
]}

Chen, Chien-Hsiun ^{[6
,7
]}

Chang, Li-Ching ^{[6
]}

Pan, Wen-Harn ^{[6
]}

Qi, Qibin ^{[25
]}

Isono, Masato ^{[3
]}

Zheng, Wei ^{[9
,10
]}

Cai, Qiuyin ^{[9
,10
]}

Gao, Yutang ^{[26
]}

Yamamoto, Ken ^{[27
]}

Ohnaka, Keizo ^{[28
]}

Takayanagi, Ryoichi ^{[29
]}

Kita, Yoshikuni ^{[30
]}

Ueshima, Hirotsugu ^{[30
,31
]}

Hsiung, Chao A. ^{[32
]}

Cui, Jinrui ^{[12
]}

Sheu, Wayne H. -H. ^{[33
,34
,35
]}

Rotter, Jerome I. ^{[36
]}

Chen, Yii-Der I. ^{[36
]}

Hsu, Chris ^{[14
]}

Okada, Yukinori ^{[37
,38
]}

Kubo, Michiaki ^{[39
]}

Takahashi, Atsushi ^{[38
]}

机构：

[1] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore

[2] Natl Univ Hlth Syst, Singapore, Singapore

[3] Natl Ctr Global Hlth & Med, Tokyo, Japan

[4] Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea

[5] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai, Peoples R China

[6] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan

[7] China Med Univ, Sch Chinese Med, Taichung, Taiwan

[8] Southeast Univ, Dept Endocrinol, Xuzhou Cent Hosp, Xuzhou Clin Sch,Xuzhou Med Coll,Affiliated Hosp, Xuzhou, Jiangsu, Peoples R China

[9] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA

[10] Vanderbilt Univ, Sch Med, Dept Med, Div Epidemiol, Nashville, TN 37212 USA

[11] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Sakyo Ku, Kyoto, Japan

[12] Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA

[13] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA

[14] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[15] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore

[16] Natl Univ Singapore, Dept Ophthalmol, Singapore 117548, Singapore

[17] Duke Natl Univ Singapore Grad Med Sch, Neurosci & Behav Disorders NBD Program, Singapore, Singapore

[18] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore

[19] Natl Univ Singapore, Dept Paediat, Singapore 117548, Singapore

[20] Duke Univ, Med Ctr, Duke Eye Ctr, Durham, NC USA

[21] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117595, Singapore

[22] Duke Natl Univ Singapore Grad Med Sch, Off Clin Sci, Ctr Quantitat Med, Singapore, Singapore

[23] Hebrew Univ Jerusalem, Sch Publ Hlth, Jerusalem, Israel

[24] Duke Natl Univ Singapore Grad Med Sch, Singapore, Singapore

[25] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA

[26] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China

[27] Kyushu Univ, Med Inst Bioregulat, Div Genom, Fukuoka 812, Japan

[28] Kyushu Univ, Grad Sch Med Sci, Dept Geriatr Med, Fukuoka 812, Japan

[29] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Fukuoka 812, Japan

[30] Shiga Univ Med Sci, Dept Hlth Sci, Otsu, Shiga 52021, Japan

[31] Shiga Univ Med Sci, Ctr Epidemiol Res Asia, Otsu, Shiga 52021, Japan

[32] Natl Hlth Res Inst, Inst Populat Hlth Sci, Zhunan, Taiwan

[33] Taichung Vet Gen Hosp, Dept Internal Med, Div Endocrine & Metab, Taichung, Taiwan

[34] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan

[35] Natl Def Med Ctr, Sch Med, Taipei, Taiwan

[36] Harbor Univ Calif, Inst Translat Genom & Biomed Sci, Los Angeles Biomed Res Inst, Los Angeles Med Ctr, Torrance, CA USA

[37] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Human Genet & Dis Divers, Tokyo, Japan

[38] RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan

[39] RIKEN Ctr Integrat Med Sci, Lab Genotyping Dev, Yokohama, Kanagawa, Japan

[40] RIKEN Ctr Integrat Med Sci, Lab Cardiovasc Dis, Yokohama, Kanagawa, Japan

[41] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[42] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA

[43] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA

[44] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[45] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA

[46] Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea

[47] Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA

[48] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA

[49] Ehime Univ, Grad Sch Med, Dept Geriatr Med, Toon, Ehime, Japan

[50] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

来源：

DIABETES | 2014年 / 63卷 / 07期

关键词：

WIDE ASSOCIATION; GENETIC-VARIATION; OXIDATIVE STRESS; COMMON VARIANTS; CELIAC-DISEASE; CELL TRAITS; METAANALYSIS; MUTATIONS; HAPLOTYPE; EXPRESSION;

D O I：

10.2337/db13-1815

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Glycated hemoglobin A(1c) (HbA(1c)) is used as a measure of glycemic control and also as a diagnostic criterion for diabetes. To discover novel loci harboring common variants associated with HbA(1c) in East Asians, we conducted a meta-analysis of 13 genome-wide association studies (GWAS; N = 21,026). We replicated our findings in three additional studies comprising 11,576 individuals of East Asian ancestry. Ten variants showed associations that reached genome-wide significance in the discovery data set, of which nine (four novel variants at TMEM79 [P value = 1.3 x 10(-23)], HBS1L/MYB [8.5 x 10(-15)], MYO9B [9.0 x 10(-12)], and CYBA [1.1 x 10(-8)] as well as five variants at loci that had been previously identified [CDKAL1, G6PC2/ABCB11, GCK, ANK1, and FN3KI]) showed consistent evidence of association in replication data sets. These variants explained 1.76% of the variance in HbA(1c). Several of these variants (TMEM79, HBS1L/MYB, CYBA, MYO9B, ANK1, and FN3K) showed no association with either blood glucose or type 2 diabetes. Among individuals with nondiabetic levels of fasting glucose (<7.0 mmol/L) but elevated HbA(1c) (>= 6.5%), 36.1% had HbA(1c) <6.5% after adjustment for these six variants. Our East Asian GWAS meta-analysis has identified novel variants associated with HbA(1c) as well as demonstrated that the effects of known variants are largely transferable across ethnic groups. Variants affecting erythrocyte parameters rather than glucose metabolism may be relevant to the use of HbA(1c) for diagnosing diabetes in these populations.

引用

页码：2551 / 2562

页数：12

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