Date: Sunday, June 12, 2016
Session Name: Poster Session B: Kidney: Cardiovascular and Metabolic
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
Purpose: New-onset diabetes after transplantation (NODAT) is associated increased mortality. Using a DNA biobank linked to electronic medical records (EMR) at Vanderbilt University (BioVU), we performed a genome wide association study (GWAS) for NODAT to help inform risk for NODAT development in kidney transplant recipients.
Methods: We identified 648 European American recipients with GWAS data genotyped on either Illumina OMNI1 or OMNI5 platforms. After standard quality control measures and removing 340 individuals with pre-existing diabetes, samples from 302 participants and 537,478 single nucleotide polymorphisms (SNPs) remained. The SNPs were imputed to the 1000 genomes cosmopolitan panel. The primary outcome was development of NODAT diagnosed by a combination of ICD-9 codes, lab values, and medications. We performed multiple logistic regression analyses to evaluate the association between common SNPs (minor allele frequency >5%) and NODAT while adjusting for age, sex, body mass index and genetic ancestry components.
Results: The cohort mean age was 42.4 years, with 59.9% female, 52 NODAT cases and 248 controls. While no SNPs passed the genome-wide significance threshold (p=5×10-8), we report suggestive evidence (p < .00001) for SNPs from 24 independent loci. Top five loci with the lowest p-values were intronic SNPs in the genes PLXDC1 (rs72823322; P=4.3×10-7), LOC105369536 (rs56072101; p=1.1×10-6), DLGAP2 (rs62488490; p=1.1×10-6), TLN2 (rs58449071; p=1.2×10-6), and NFATC2 (rs11698388; p=1.6×10-6). Additionally, noteworthy gene loci with potential biological ties included CNTNAP2 (rs68002961; p=7.8×10-6) and BICD1 (rs2630577; p=8.5×10-6). SNPs in CNTNAP2 have been reported to be marginally associated with adiponectin levels (rs10500165) and diabetes (rs10952650). rs10952650 was nominally associated with NODAT in our dataset as well (p=0.04). SNPs in BICD1 have been previously associated with pancreatic neoplasms. Evaluation of candidate SNPs for NODAT previously noted in the literature were not replicated in this study, except for a small signal in the PPARG gene (rs1801282; p= 0.055).
Conclusions: We found several suggestive gene loci in relation to NODAT, some with close biological relevance. Further evaluation in larger sample sizes is warranted.
CITATION INFORMATION: Giri A, Sanders M, Velez Edwards D, Ikizler T, Roden D, Birdwell K. A Genome Wide Association Study of New Onset Diabetes After Transplant in Kidney Transplantation. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Giri A, Sanders M, Velez D, Ikizler T, Roden D, Birdwell K. A Genome Wide Association Study of New Onset Diabetes After Transplant in Kidney Transplantation. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/a-genome-wide-association-study-of-new-onset-diabetes-after-transplant-in-kidney-transplantation/. Accessed July 21, 2018.
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