Genome-wide variants and polygenic risk scores for cognitive impairment following blood or marrow transplantation. Bone Marrow Transplant 2022 Jun;57(6):925-933
Date
04/06/2022Pubmed ID
35379913Pubmed Central ID
PMC9233077DOI
10.1038/s41409-022-01642-5Scopus ID
2-s2.0-85127536986 (requires institutional sign-in at Scopus site)Abstract
Cognitive impairment is prevalent in blood or marrow transplantation (BMT) recipients, albeit with inter-individual variability. We conducted a genome-wide association study of objective cognitive function assessed longitudinally in 239 adult BMT recipients for discovery and replicated in an independent cohort of 540 BMT survivors. Weighted genome-wide polygenic risk scores (PRS) were constructed using linkage disequilibrium pruned significant SNPs. Forty-four genome-wide significant SNPs were identified using additive (n = 3); codominant (n = 20) and genotype models (n = 21). Each additional copy of a risk allele was associated with a 0.28-point (p = 1.07 × 10-8) to a 1.82-point (p = 6.7 × 10-12) increase in a global deficit score. We replicated two SNPs (rs11634183 and rs12486041) with links to neural integrity. Patients in the top PRS quintile were at increased risk of cognitive impairment in discovery (RR = 1.95, 95%CI: 1.28-2.96, p = 0.002) and replication cohorts (OR = 1.84, 95%CI, 1.02-3.32, p = 0.043). Associations were stronger among individuals with lowest clinical risk for cognitive impairment. These findings support potential utility of PRS-based risk classification in the development of targeted interventions aimed at improving cognitive outcomes in BMT survivors.
Author List
Sharafeldin N, Zhang J, Singh P, Bosworth A, Chen Y, Patel SK, Wang X, Francisco L, Forman SJ, Wong FL, Ojesina AI, Bhatia SAuthor
Akinyemi Ojesina MD, PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultBone Marrow
Cognitive Dysfunction
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Multifactorial Inheritance
Polymorphism, Single Nucleotide
Risk Factors
