Work

Using a Bayesian Hierarchical Model for Identifying Single Nucleotide Polymorphisms Associated with Childhood Acute Lymphoblastic Leukemia Risk in Case-Parent Triads

Year: 2013

Type: article

Abstract: Childhood acute lymphoblastic leukemia (ALL) is a condition that arises from complex etiologies. The absence of consistent environmental risk factors and the presence of modest familial associations suggest ALL is a complex trait with an underlying genetic component. The identification of genetic factors associated with disease is complicated by complex genetic covariance structures and multiple testing issues. Both issues can be resolved with appropriate Bayesian variable selection methods. The present study was undertaken to extend our hierarchical Bayesian model for case-parent triads to incorporate single nucleotide polymorphisms (SNPs) and incorporate the biological grouping of SNPs within genes. Based on previous evidence that genetic variation in the folate metabolic pathway influences ALL risk, we evaluated 128 tagging SNPs in 16 folate metabolic genes among 118 ALL case-parent triads recruited from the Texas Children's Cancer Center (Houston, TX) between 2003 and 2010. We used stochastic search gene suggestion (SSGS) in hierarchical Bayesian models to evaluate the association between folate metabolic SNPs and ALL. Using Bayes factors among these variants in childhood ALL case-parent triads, two SNPs were identified with a Bayes factor greater than 1. There was evidence that the minor alleles of NOS3 rs3918186 (OR = 2.16; 95% CI: 1.51-3.15) and SLC19A1 rs1051266 (OR = 2.07; 95% CI: 1.25-3.46) were positively associated with childhood ALL. Our findings are suggestive of the role of inherited genetic variation in the folate metabolic pathway on childhood ALL risk, and they also suggest the utility of Bayesian variable selection methods in the context of case-parent triads for evaluating the role of SNPs on disease risk.

Source: PLoS ONE

DOI: 10.1371/journal.pone.0084658

Authors: Ying Cao, Philip J. Lupo, Michael D. Swartz, Darryl Nousome, Michael E. Scheurer

Institution: Baylor College of Medicine

Language: English

Topic: Acute Lymphoblastic Leukemia research

Subfield: Public Health, Environmental and Occupational Health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,382