Association analysis of copy number variations in type 2 diabetes-related susceptible genes in a Chinese population

被引:8
作者
Yan, Yu-Xiang [1 ,2 ]
Li, Jia-Jiang-Hui [1 ]
Xiao, Huan-Bo [3 ]
Wang, Shuo [1 ]
He, Yan [1 ,2 ]
Wu, Li-Juan [1 ,2 ]
机构
[1] Capital Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, 10 Xitoutiao, Beijing 100069, Peoples R China
[2] Municipal Key Lab Clin Epidemiol, Beijing, Peoples R China
[3] Capital Med Univ, Dept Prevent Med, Yanjing Med Coll, Beijing, Peoples R China
关键词
Type; 2; diabetes; Copy number variations; Association; Interaction; ZINC TRANSPORTER ZNT8; GLUCOSE-HOMEOSTASIS; INSULIN-RESISTANCE; GENOME; EXPRESSION; VARIANTS; DISEASE; METAANALYSIS; PHENOTYPES; SECRETION;
D O I
10.1007/s00592-018-1168-1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Copy number variations (CNVs) have been implicated as an important genetic marker of common disease. In this study, we explored genetic effects of common CNVs in Type 2 diabetes (T2D) related susceptible genes in Chinese population. Seven common CNV loci were selected from genes enclosing the susceptible single nucleotide polymorphisms (SNPs) of T2D confirmed by genome-wide association studies (GWAS) and replication studies conducted in east Asia population. The CNVs and SNPs were genotyped in 504 T2D patients and 494 non-T2D controls. Cumulative effect of the positive CNV loci was measured using genetic risk score (GRS). Multiplicative and additive interaction between candidate CNV loci and SNPs were assessed. Compared with the common two copies, the deletion of nsv6360 (adjusted OR = 2.28, 95% CI 1.37-3.78, P = 0.001), nsv8414 (adjusted OR = 1.89, 95% CI 1.16-3.08, P = 0.006) and nsv1898 (adjusted OR = 1.84, 95% CI 1.19-2.84, P = 0.005) were significantly associated with increased risk of T2D (P < 0.007). Significant dose-response relationship was observed between GRS and the risk of T2D (chi (2) for trend = 19.51, P < 0.001). In addition, significant additive interactions between nsv8414 and rs17584499 in PTPRD (AP = 0.60, 95% CI 0.12-1.07) and nsv1898 and rs16955379 in CMIP (AP = 0.46, 95% CI 0.01-0.91) were observed. There were three CNV loci (nsv6360, nsv8414 and nsv1898) associated with T2D, and a significant cumulative effect of these loci on the risk of T2D. The comprehensive effects of both CNVs and SNPs may provide a more useful tool for the identification of genetic susceptibility for T2D.
引用
收藏
页码:909 / 916
页数:8
相关论文
共 33 条
[1]   Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables [J].
Ahlqvist, Emma ;
Storm, Petter ;
Karajamaki, Annemari ;
Martinell, Mats ;
Dorkhan, Mozhgan ;
Carlsson, Annelie ;
Vikman, Petter ;
Prasad, Rashmi B. ;
Aly, Dina Mansour ;
Almgren, Peter ;
Wessman, Ylva ;
Shaat, Nael ;
Spegel, Peter ;
Mulder, Hindrik ;
Lindholm, Eero ;
Melander, Olle ;
Hansson, Ola ;
Malmqvist, Ulf ;
Lernmark, Ake ;
Lahti, Kaj ;
Forsen, Tom ;
Tuomi, Tiinamaija ;
Rosengren, Anders H. ;
Groop, Leif .
LANCET DIABETES & ENDOCRINOLOGY, 2018, 6 (05) :361-369
[2]   Calculating measures of biological interaction [J].
Andersson, T ;
Alfredsson, L ;
Källberg, H ;
Zdravkovic, S ;
Ahlbom, A .
EUROPEAN JOURNAL OF EPIDEMIOLOGY, 2005, 20 (07) :575-579
[3]  
[Anonymous], 1999, DEF DIAGN CLASS DIAB
[4]   Meta-analysis of the Gly482Ser variant in PPARGC1A in type 2 diabetes and related phenotypes [J].
Barroso, I ;
Luan, J ;
Sandhu, MS ;
Franks, PW ;
Crowley, V ;
Schafer, AJ ;
O'Rahilly, S ;
Wareham, NJ .
DIABETOLOGIA, 2006, 49 (03) :501-505
[5]   Meta-analysis and functional effects of the SLC30A8 rs13266634 polymorphism on isolated human pancreatic islets [J].
Cauchi, Stephane ;
Del Guerra, Silvia ;
Choquet, Helene ;
D'Aleo, Valentina ;
Groves, Christopher J. ;
Lupi, Roberto ;
McCarthy, Mark I. ;
Froguel, Philippe ;
Marchetti, Piero .
MOLECULAR GENETICS AND METABOLISM, 2010, 100 (01) :77-82
[6]   Replication of genome-wide association signals of type 2 diabetes in Han Chinese in a prospective cohort [J].
Chang, Yi-Cheng ;
Chiu, Yen-Feng ;
Liu, Pi-Hua ;
Shih, Kuang-Chung ;
Lin, Ming-Wei ;
Sheu, Wayne H. -H. ;
Quertermous, Thomas ;
Curb, Jess David ;
Hsiung, Chano A. ;
Lee, Wei-Jei ;
Lee, Po-Chu ;
Chen, Yuan-Tsong ;
Chuang, Lee-Ming .
CLINICAL ENDOCRINOLOGY, 2012, 76 (03) :365-372
[7]   PTPRD silencing by DNA hypermethylation decreases insulin receptor signaling and leads to type 2 diabetes [J].
Chen, Yng-Tay ;
Lin, Wei-De ;
Liao, Wen-Lin ;
Lin, Ying-Ju ;
Chang, Jan-Gowth ;
Tsai, Fuu-Jen .
ONCOTARGET, 2015, 6 (15) :12997-13005
[8]   In vivo expression and functional characterization of the zinc transporter ZnT8 in glucose-induced insulin secretion [J].
Chimienti, Fabrice ;
Devergnas, Severine ;
Pattou, Francois ;
Schuit, Frans ;
Garcia-Cuenca, Rachel ;
Vandewalle, Brigitte ;
Kerr-Conte, Julie ;
Van Lommel, Leentje ;
Grunwald, Didier ;
Favier, Alain ;
Seve, Michel .
JOURNAL OF CELL SCIENCE, 2006, 119 (20) :4199-4206
[9]   Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians [J].
Cho, Yoon Shin ;
Chen, Chien-Hsiun ;
Hu, Cheng ;
Long, Jirong ;
Ong, Rick Twee Hee ;
Sim, Xueling ;
Takeuchi, Fumihiko ;
Wu, Ying ;
Go, Min Jin ;
Yamauchi, Toshimasa ;
Chang, Yi-Cheng ;
Kwak, Soo Heon ;
Ma, Ronald C. W. ;
Yamamoto, Ken ;
Adair, Linda S. ;
Aung, Tin ;
Cai, Qiuyin ;
Chang, Li-Ching ;
Chen, Yuan-Tsong ;
Gao, Yutang ;
Hu, Frank B. ;
Kim, Hyung-Lae ;
Kim, Sangsoo ;
Kim, Young Jin ;
Lee, Jeannette Jen-Mai ;
Lee, Nanette R. ;
Li, Yun ;
Liu, Jian Jun ;
Lu, Wei ;
Nakamura, Jiro ;
Nakashima, Eitaro ;
Ng, Daniel Peng-Keat ;
Tay, Wan Ting ;
Tsai, Fuu-Jen ;
Wong, Tien Yin ;
Yokota, Mitsuhiro ;
Zheng, Wei ;
Zhang, Rong ;
Wang, Congrong ;
So, Wing Yee ;
Ohnaka, Keizo ;
Ikegami, Hiroshi ;
Hara, Kazuo ;
Cho, Young Min ;
Cho, Nam H. ;
Chang, Tien-Jyun ;
Bao, Yuqian ;
Hedman, Asa K. ;
Morris, Andrew P. ;
McCarthy, Mark I. .
NATURE GENETICS, 2012, 44 (01) :67-U97
[10]   Numerous Genes in Loci Associated With Body Fat Distribution Are Linked to Adipose Function [J].
Dahlman, Ingrid ;
Ryden, Mikael ;
Brodin, David ;
Grallert, Harald ;
Strawbridge, Rona J. ;
Amer, Peter .
DIABETES, 2016, 65 (02) :433-437