Genome-wide meta-analysis in Japanese populations identifies novel variants at the TMC6-TMC8 and SIX3-SIX2 loci associated with HbA1c

被引：26

作者：

Hachiya, Tsuyoshi ^{[1
]}

Komaki, Shohei ^{[1
]}

Hasegawa, Yutaka ^{[2
]}

Ohmomo, Hideki ^{[1
]}

Tanno, Kozo ^{[3
,4
]}

Hozawa, Atsushi ^{[5
]}

Tamiya, Gen ^{[6
]}

Yamamoto, Masayuki ^{[6
]}

Ogasawara, Kuniaki ^{[7
,8
]}

Nakamura, Motoyuki ^{[7
,9
]}

Hitomi, Jiro ^{[7
,10
]}

Ishigaki, Yasushi ^{[2
,11
]}

Sasaki, Makoto ^{[7
,12
]}

Shimizu, Atsushi ^{[1
]}

机构：

[1] Iwate Med Univ, Disaster Reconstruct Ctr, Iwate Tohoku Med Megabank Org, Div Biomed Informat Anal, 2-1-1 Nishitokuta, Shiwa, Iwate 0283694, Japan

[2] Iwate Med Univ, Sch Med, Dept Internal Med, Div Diabet & Metab, 19-1 Uchimaru, Morioka, Iwate 0208505, Japan

[3] Iwate Med Univ, Disaster Reconstruct Ctr, Iwate Tohoku Med Megabank Org, Div Clin Res & Epidemiol, 2-1-1 Nishitokuta, Shiwa, Iwate 0283694, Japan

[4] Iwate Med Univ, Sch Med, Dept Hyg & Prevent Med, 19-1 Uchimaru, Morioka, Iwate 0208505, Japan

[5] Tohoku Univ, Tohoku Med Megabank Org, Prevent Med & Epidemiol, 2-1 Seiryo, Sendai, Miyagi 9808573, Japan

[6] Tohoku Univ, Tohoku Med Megabank Org, Integrat Gen, 2-1 Seiryo, Sendai, Miyagi 9808573, Japan

[7] Iwate Med Univ, Disaster Reconstruct Ctr, Iwate Tohoku Med Megabank Org, 2-1-1 Nishitokuta, Shiwa, Iwate 0283694, Japan

[8] Iwate Med Univ, Sch Med, Dept Neurosurg, 19-1 Uchimaru, Morioka, Iwate 0208505, Japan

[9] Iwate Med Univ, Sch Med, Dept Internal Med, 19-1 Uchimaru, Morioka, Iwate 0208505, Japan

[10] Iwate Med Univ, Sch Med, Dept Anat, 2-1-1 Nishitokuda, Yahaba, Iwate 0283694, Japan

[11] Iwate Med Univ, Disaster Reconstruct Ctr, Iwate Tohoku Med Megabank Org, Div Innovat & Educ, 2-1-1 Nishitokuta, Shiwa, Iwate 0283694, Japan

[12] Iwate Med Univ, Inst Biomed Sci, Div Ultrahigh Field MRI, 2-1-1 Nishitokuta, Yahaba, Iwate 0283694, Japan

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

POLYUNSATURATED FATTY-ACIDS; GLYCATED HEMOGLOBIN; GENETIC ARCHITECTURE; GLYCOSYLATION GAP; 14-3-3; PROTEINS; BLOOD-GLUCOSE; HERITABILITY; RISK; HBA1C; ARYLFORMAMIDASE;

D O I：

10.1038/s41598-017-16493-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Glycated haemoglobin (HbA(1c)) is widely used as a biomarker for the diagnosis of diabetes, for population-level screening, and for monitoring the glycaemic status during medical treatment. Although the heritability of HbA(1c) has been estimated at similar to 55-75%, a much smaller proportion of phenotypic variance is explained by the HbA(1c)-associated variants identified so far. To search for novel loci influencing the HbA(1c) levels, we conducted a genome-wide meta-analysis of 2 non-diabetic Japanese populations (n = 7,704 subjects in total). We identified 2 novel loci that achieved genome-wide significance: TMC6-TMC8 (P = 5.3 x 10(-20)) and SIX3-SIX2 (P = 8.6 x 10(-9)). Data from the largest-scale European GWAS conducted for HbA(1c) supported an association between the novel TMC6-TMC8 locus and HbA1c (P = 2.7 x 10(-3)). The association analysis with glycated albumin and glycation gap conducted using our Japanese population indicated that the TMC6-TMC8 and SIX3-SIX2 loci may influence the HbA1c level through non-glycaemic and glycaemic pathways, respectively. In addition, the pathwaybased analysis suggested that the linoleic acid metabolic and 14-3-3-mediated signalling pathways were associated with HbA(1c). These findings provide novel insights into the molecular mechanisms that modulate the HbA(1c) level in non-diabetic subjects.

引用

页数：11

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