Association analysis of copy number variations in type 2 diabetes-related susceptible genes in a Chinese population
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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 (χ2 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.
KeywordsType 2 diabetes Copy number variations Association Interaction
This study was supported by the National Natural Science Foundation (81573214, 81773511), the Beijing Municipal Natural Science Foundation (7162020).
Compliance with ethical standards
Conflict of interest
The authors declares that they have no conflict of interest.
This experiment was approved by the Ethics Committee of Capital Medical University. This study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki. All subjects signed informed consent forms.
Human and animal rights
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.
Informed consent was obtained from all patients for being included in the study.
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