Associations of Germline Genetic Variants with Depression and Fatigue among Hematologic Cancer Patients Treated with Allogeneic Hematopoietic Cell Transplantation.

OBJECTIVE: Depression and fatigue are common among cancer patients and are associated with germline genetic variation. The goal of this pilot study was to examine genetic associations with depression and fatigue in the year after allogeneic HCT.

METHODS: Blood was collected from patients and their donors prior to HCT. Patients completed self-report measures of depression and fatigue prior to HCT (T1), 90 days post-HCT (T2), and one year post-HCT (T3). Of the 384 genetic variants genotyped on a custom Illumina BeadChip microarray, 267 were retained for analysis based on quality control. Main effects of patient and donor variants as well as their interaction were examined using regression analyses. Significant variants were defined as those with a false discovery rate adjusted p value of <0.05.

RESULTS: The sample consisted of 59 patient-donor pairs. Mean levels of depression and fatigue did not change significantly over time (p-values>.41). Increases in depression from T1 to T2 were associated with patient-donor interactions at rs1928040 (p = 3.0x10-4) and rs6311 (p = 2.0x10-4) in HTR2A. Increases in fatigue from T1 to T2 were associated with patient rs689021 in SORL1 (p = 6.0x10-5) and a patient-donor interaction at rs1885884 in HTR2A (p < 1.0x10-4).

CONCLUSIONS: Data suggest that variants in genes regulating the serotonergic system (HTR2A) and lipid metabolism (SORL1) are associated with changes in depression and fatigue in allogeneic HCT patients, implicating patients' own genetic inheritance as well as that of donors. Additional studies are warranted to confirm these findings.