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Genomewide association study reveals novel genetic loci associated with change in renal function in heart transplant recipients
Author(s) -
Asleh Rabea,
Snipelisky David,
Hathcock Matthew,
Kremers Walter,
Liu Duan,
Batzler Anthony,
Jenkins Gregory,
Kushwaha Sudhir,
Pereira Naveen L.
Publication year - 2018
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/ctr.13395
Subject(s) - genome wide association study , medicine , single nucleotide polymorphism , renal function , genetic association , transplantation , kidney transplantation , calcineurin , genotyping , confounding , genetics , oncology , bioinformatics , genotype , biology , gene
Background Renal dysfunction occurs commonly after heart transplantation ( HT x) with wide inter‐individual variability but whether a genetic predisposition exists in these patients is unknown. Genomewide association studies ( GWAS ) have not been performed to assess the association of genetic variation with change in renal function after HT x. Methods Clinical and demographic data of patients who underwent HT x and provided blood samples and consent for genetic analysis were included. Genotyping was performed using Illumina Infinium Human CoreExome v1.0 analysis kit. A GWAS utilizing linear regression models was performed with estimated glomerular filtration rate ( eGFR ) at 1 year as the phenotype after adjusting for baseline eGFR prior to HT x and conversion from calcineurin inhibitor to sirolimus as primary immunosuppression therapy. Results A total of 251 HT x recipients were genotyped for 314,903 single nucleotide polymorphisms ( SNP s). The mean ( SD ) age was 50 (12.5) years; most patients were of European origin (n = 243, 96.8%) and males (n = 179, 71.3%). After adjustment for potential confounders, two variants, rs17033285 ( P = 4.3 × 10 −7 ) and rs4917601 ( P = 6.46 × 10 −7 ), in a long non‐coding RNA (lnc RNA ) gene LINC 01121 and a pseudogene BTBD 7P2 , were identified to have a significant association with change in GFR at 1 year after HT x. Conclusions Our first of its kind GWAS demonstrates that genetic variation affects renal function after HT x independent of other risk factors. Agnostic genetic approaches such as these may lead to identification of novel biological pathways such as the role of lnc RNA s in the development of renal dysfunction post‐ HT x.