Association analysis of copy number variations in type 2 diabetes-
related susceptible genes in a Chinese population
· Jia‑Jiang‑Hui Li
· Huan‑Bo Xiao
· Shuo Wang
· Yan He
· Li‑Juan Wu
Received: 27 February 2018 / Accepted: 25 May 2018
© Springer-Verlag Italia S.r.l., part of Springer Nature 2018
Aims 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.
Methods 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.
Results 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 (χ
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.
Conclusions 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.
Keywords Type 2 diabetes · Copy number variations · Association · Interaction
Type 2 diabetes (T2D) has been identiﬁed as a major world-
wide public health problem, aﬀecting around 400 million
people globally with high rates of diabetes-related morbidity
and mortality . This phenomenon is particularly evident
in inland China, which has the prevalence of 11.6% for dia-
betes in adults . In addition to behavioral disturbances,
dietary deﬁciency and increased adiposity, genetic compo-
nent also play an important role in the pathogenesis of T2D.
Genome-wide association studies (GWAS) and large-
scale genotyping studies have identiﬁed more than 90 risk
loci associated with T2D in Asian and European populations
[3, 4]. Despite single nucleotide polymorphisms (SNPs)
provided valuable insights into the genetic basis of T2D,
a large proportion of the heritability remains unexplained,
suggesting that additional studies are required to discover
the “missing heritability” .
Managed by Massimo Porta.
Electronic supplementary material The online version of this
article (https ://doi.org/10.1007/s0059 2-018-1168-1) contains
supplementary material, which is available to authorized users.
* Yu-Xiang Yan
* Li-Juan Wu
Department of Epidemiology and Biostatistics,
School of Public Health, Capital Medical University,
No. 10 Xitoutiao, You An Men, Beijing 100069,
People’s Republic of China
Municipal Key Laboratory of Clinical Epidemiology,
Beijing, People’s Republic of China
Department of Preventive Medicine, Yanjing Medical
College, Capital Medical University, Beijing,
People’s Republic of China