Diabetes Research and Clinical Practice - Volume 120 - Supplement 1 - October 2016

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influence the binding of miRNAs, and 4 T2D lead SNPs and 8
proxy SNPs were identified as PhosSNPs that might affect
protein phosphorylation. The effect of these T2D-associated
GWAS SNPs on miRNAs and transcription factor binding are
currently being experimentally tested in our lab.
GO analysis showed that most of the T2D related genes were
enriched in the biological regulation process and binding
function. Pathway enrichment analysis confirmed 2 well-
known maturity onset diabetes of the young and T2D path-
ways. PPI network analysis identified highly interconnected
“ hub” genes TCF7L2, MTNR1B, SLC30A8, CDKAL1, IGF2BP2,
CDC123 and KCNJ11 and FTO, HHEX and HNF1B THADA,
JAZF1, CAMK1D and WFS1 and TSPAN8 that created 2 tight
subnetwork
OL04-6
Association between GWAS-identified variants with CKD in
Chinese with Type 2 Diabetes: The Hong Kong Diabetes
Registry
F.Y. XIE 1*, G.Z. JIANG1, C.H. TAM1, A.O. LUK1, H.M. LEE 1,
C.K. LIM 1, A.P. KONG1, H.Y. LAN1,2, C.C. SZETO1, W.Y. SO1,3,
J.C. CHAN 1–3, R.C. MA1–4. 1Department of Medicine and
Therapeutics, The Chinese University of Hong Kong, 2Li Ka Shing
Institute of Health Sciences, The Chinese University of Hong Kong,
3 Hong Kong Institute of Diabetes and Obesity, The Chinese University
of Hong Kong, 4Integrated Bioinformatics Laboratory for Cancer
Biology and Metabolic Diseases, The Chinese University of Hong
Kong, Hong Kong
Background and objectives: Chronic kidney disease (CKD) is an
important complication in patients with diabetes and signifi-
cant heritability has been noted. Recent genome-wide associ-
ation studies (GWAS) have identified a number of single
nucleotide polymorphisms (SNPs) associated with CKD and
renal function traits. However, the majority of these variants
were identified from studies involving Caucasians and African
Americans, with few studies conducted in Asians or involving
patients with diabetes. We conducted a replication study to
examine whether these SNPs are associated with the risk of
developing CKD in Chinese patients with type 2 diabetes (T2D).
Subjects and methods: We performed a nested case-control
study within the Hong Kong Diabetes Registry. Genome-wide
genotyping was conducted for each subject using the Illumina
Omni 2.5+ exome array and genotype data was imputed using
minimac 3 with the 1000 Genomes Project phase 3 v5 as
reference panel. After standard quality control, a total of 5730
Chinese type 2 diabetic patients were included, including
2881 patients were with pre-existing or incident CKD, and
2849 free of CKD. Through literature review, a total of 77
GWAS-identified SNPs were retrieved from previous publica-
tions as being significantly associated with CKD or renal
function traits. We conducted in silico look-up to investigate
associations between these known SNPs and CKD in T2D
utilizing logistic regression and an additive model.
Results: The mean age of all subjects was 57.5 ± 12.9 years,
45.7% male, median duration of diabetes was 6 [interquartile
range: 2 –11] years, and 29% had diabetic retinopathy at base-
line. After adjustment for age, gender and principal compo-
nents, among the 77 known SNPs, the directly-genotyped
variant rs881858 near VEGFA (OR = 0.886, 95% CI 0.805 –0.974,
P = 0.012) was significantly associatedwithCKD inChinese T2D
patient. An imputed SNP rs266734 also showed significant
associationwith CKD (OR = 0.695, 95%CI 0.522 –0.925, p = 0.012).
The observed effect was consistent with the direction from
previous reported findings. Excluding 8 SNPS with poor quality
of imputation, the remaining 67 SNPsdidnot exhibit significant
associations with CKD in Chinese with T2D.
Conclusions: Among 77 known GWAS-identified SNPs for
kidney diseases, we identified significant association between
rs881858 and CKD in Chinese patients with T2D. The
discrepancies may be related to different ethnicity as well as
the group of subjects being studied (general population vs.
subjects with T2D). Our results highlight the need to perform
studies in the relevant ethnic group in order to uncover the
genetic susceptibility of diabetic kidney disease.
OL04-7
Genome-wide association study in Chinese identifies new
susceptibility loci associated with chronic kidney disease in
type 2 diabetes
Guozhi JIANG1, Claudia HT TAM1, Andrea O LUK1,
Heung Man LEE1, Cadmon KP LIM1, Xiaodan FAN3, Si LOK4,
Ting Fung CHAN5, Kevin Yuk-Lap YIP 6, Nelson TANG4,
Stephen KW TSUI7, Weichuan YU8, Brian TOMLINSON1 ,
Yu HUANG7, Huiyao LAN1,9, Cheuk-Chun SZETO 1,
Wing Yee SO1,2, Juliana C.N. CHAN1,2,9, Ronald C.W. MA1,2,9*.
1Department of Medicine and Therapeutics, The Chinese University of
Hong Kong, 2Hong Kong Institute of Diabetes and Obesity, The
Chinese University of Hong Kong, 3Department of Statistics, The
Chinese University of Hong Kong, 4Department of Chemical
Pathology, The Chinese University of Hong Kong, 5School of Life
Sciences, The Chinese University of Hong Kong, 6Department of
Computer Science and Engineering, The Chinese University of Hong
Kong,7School of Biomedical Sciences, The Chinese University of Hong
Kong, 8Department of Electronic and Computer Engineering, HKUST,
9Li Ka Shing Institute of Health Sciences, The Chinese University of
Hong Kong, China
Background and aims: Diabetic kidney disease is a major
complication of diabetes and the leading cause of end-stage
renal disease in most parts of the world. Although a few
common susceptibility variants have been identified by
several genome-wide association studies (GWAS) recently,
much of the inherited predisposition to diabetic kidney
disease remains unexplained. To unravel the genetic basis of
this important complication, we performed a nested case-
control study for chronic kidney disease (CKD) in type 2
diabetes (T2D) from the Hong Kong Diabetes Registry (HKDR).
Materials and methods: More than 8,000 patients with T2D
and prospective follow-up were included in the HKDR. eGFR
was calculated according to the Chinese Modification of
Diet in Renal Disease (MDRD) equation. CKD was defined (i)
Diabetes with renal manifestations (ICD-9 code: 250.4), chronic
kidney disease (ICD-9 code: 585), or unspecified renal failure
(ICD-9 code: 586) or (ii) dialysis (ICD-9 procedure code: 39.95)
or peritoneal dialysis (ICD-9 procedure code: 54.98) or (iii)
eGFR < 60 mL/min per 1.73 m2 during follow-up period.
Samples were genotyped using the Illumina Omni 2.5+
exome array and genotype data was imputed using minimac
3 with the 1000 Genomes Project phase 3 v5 as reference panel.
After standard quality control, ∼ 8 million common SNPs were
included in the final analysis. Association analysis was
adjusted for age, gender, and principal components.
Results: After sample QC, we included 2881 case subjects with
T2D and CKD, and 2849 control subjects with T2D duration of
>10 years but free of CKD in the genome-wide association
analysis (mean age of all subjects 57.5 ± 12.9 years, 45.7%male,
median duration of diabetes 6 [interquartile range: 2–11] years,
and 29% with retinopathy at baseline). We identified 22 SNPs
with suggestive association with CKD in T2D (p < 10−5), with
one of the strongest signal from a SNP on chromosome 9, OR
0.73 (95%CI 0.65–0.83, p = 9.98 × 10 −7), with other top suggestive
association signals from loci on chromosomes 1, 2, 4, 7, 11, 14,
16, 17, 18, 19.
Conclusions: Our study has identified a number of novel
regions associated with CKD in T2D. Additional genotyping
and integrative analysis together with methylation data are
currently in progress.
Funding acknowledgment: Supported by a Theme-based
Research Scheme from the Research Grants Council of the
Hong Kong Administrative Region, China (Project no: T12-402/
Oral Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S40–S64 S49