Genome-wide variants and polygenic risk scores for cognitive impairment following blood or marrow transplantation.
Noha SharafeldinJianqing ZhangPurnima SinghAlysia BosworthYanjun ChenSunita K PatelXuexia WangLiton FranciscoStephen J FormanF Lennie WongAkinyemi I OjesinaSmita BhatiaPublished in: Bone marrow transplantation (2022)
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.
Keyphrases
- genome wide
- cognitive impairment
- dna methylation
- copy number
- gene expression
- magnetic resonance
- end stage renal disease
- ejection fraction
- bone marrow
- machine learning
- stem cells
- physical activity
- metabolic syndrome
- chronic kidney disease
- drug delivery
- skeletal muscle
- wastewater treatment
- hepatitis c virus
- patient reported outcomes
- single cell
- human immunodeficiency virus
- childhood cancer