Genetic Risk Factors of Post-traumatic Stress Disorders in Solid Organ Transplant Recipients
Medical post-traumatic stress disorder (PTSD) can be triggered by any number of surgical or medical interventions or critical illness. For example, patients awaiting a solid organ transplant face the ever-present threat of death if a matching organ does not become available; following transplantation, they live with the ongoing risk of organ rejection. Currently, we are unable to accurately predict who will suffer from PTSD or other neuropsychiatric symptoms following transplantation. However, certain genetic variants have been associated with PTSD in the general population, and could serve as susceptibility factors for the transplant population. In this project, we are testing whether these variants can help us understand if, how, and why certain patients will develop PTSD and other neuropsychiatric symptoms following solid organ transplantation.
Need/Problem: Relative to the general population, the medically ill are at increased risk for post-traumatic stress disorder (PTSD). For example, it has been estimated that up to 17% of solid organ transplant recipients will suffer from PTSD. Patient awaiting a solid organ transplant have failed all other medical therapies and face the threat of death if a matching organ does not become available. However, only a portion of patients will develop PTSD following solid organ transplant, and medical providers struggle to anticipate who will develop this disorder.
Grant Summary: We will investigate if genetic factors, which are currently associated with PTSD, depression and chronic pain following a trauma in the general population, are associated with an increased risk of PTSD, depression and chronic pain following solid organ transplantation.
Goals and Projected Outcomes: Our goal is to better anticipate who will benefit from additional psychological support following solid organ transplantation, in order to improve these recipients’ mental health and overall post-transplantation survival.
Rebekah Nash, MD, Ph.D.
Grant Details: We will genotype ~650 individuals who underwent solid organ transplantation at UNC Hospitals between April 2014 – Sept 2018 using Genone-Wide Association Study (GWAS)-style arrays. We will perform a retrospective chart review of the same population of ~650 adult solid organ recipients. During the chart review, we will abstract clinical outcomes data including medication use, diagnoses, pain scores, and select lab results, as well as duration of time on organ wait list and demographic information. From the genotyping results, we will extract data pertaining to the minor allele frequency (MAF) of 9 single nucleotide polymorphisms (SNPs): 5-HTR2A (rs6311), FKBP5 (rs3800373, rs1360780), ADCYAP1R1 (rs2267735), RGS2 (rs4606), NR3C2 (rs5522), CRHR1 (rs242939), BDNF (rs6265), TLL1 (rs6812849). We will then determine if a statistically significant relationship exists between each SNP and the presence of PTSD, depression and/or chronic pain in the solid organ recipient population. Following our analysis of each SNP, we will calculate three polygenic risk scores for each individual, including one polygenic risk score (PRS) for PTSD, one for Major Depressive Disorder, and one for Schizophrenia. We will then assess how much variance in our clinical outcomes are explained by each PRS.