Citations 2
Identification of Two Genetic Loci Associated with Leukopenia after Chemotherapy in Patients with Breast Cancer
Fasching, Peter A. , Liu, Duan , Scully, Steve, Ingle, James N. , Lyra, Paulo C. , Rack, Brigitte , Hein, Alexander , Ekici, Arif B. , Reis, André , Schneeweiß, Andreas , Tesch, Hans , Heinrich, Georg, Beckmann, Matthias W. , Ruebner, Matthias , Huebner, Hanna , Lambrechts, Diether , Madden, Ebony , Shen, Jess, Romm, Jane, Doheny, Kim, Jenkins, Gregory D. , Cunningham, Julie M. , Janni, Wolfgang , Schaid, Daniel J. , Häberle, Lothar , Weinshilboum, Richard M. , Wang, Liewei , Lambrechts, Diether , Lambrechts, Diether , Li, Liang , Fridley, Brooke L , Cunningham, Julie M , Janni, Wolfgang , Monteiro, Alvaro N , Ingle, J , Lambrechts, Diether , Hein, Alexander , Ekici, Arif B , Reis, André , Morais Lyra, Paulo Cilas , Liu, Duan , Fehm, Tanja , Carlson, Erin E. , Li, Liang , Fridley, Brooke L. , Monteiro, Álvaro N.A. , Weinshilboum, Richard M.
Clinical Cancer Research | June 27, 2022 | Volume: 28 | Issue: 15 | Pages: 3342-3355
Abstract Purpose: To identify molecular predictors of grade 3/4 neutropenic or leukopenic events (NLE) after chemotherapy using a genome-wide association study (GWAS). Experimental Design: A GWAS was performed on patients in the phase III chemotherapy study SUCCESS-A (n = 3,322). Genotyping was done using the Illumina HumanOmniExpress-12v1 array. Findings were functionally validated with cell culture models and the genotypes and gene expression of possible causative genes were correlated with clinical treatment response and prognostic outcomes. Results: One locus on chromosome 16 (rs4784750; NLRC5; P = 1.56E-8) and another locus on chromosome 13 (rs16972207; TNFSF13B; P = 3.42E-8) were identified at a genome-wide significance level. Functional validation revealed that expression of these two genes is altered by genotype-dependent and chemotherapy-dependent activity of two transcription factors. Genotypes also showed an association with disease-free survival in patients with an NLE. Conclusions: Two loci in NLRC5 and TNFSF13B are associated with NLEs. The involvement of the MHC I regulator NLRC5 implies the possible involvement of immuno-oncological pathways.
Genome-Wide Association Analysis of Ischemic Stroke in Young Adults
Cheng, Yu-Ching , O’Connell, Jeffrey R. , Dueker, Nicole , McArdle, Patrick F. , Sparks, Mary J., Shen, Jess, Laurie, Cathy C. , Doheny, Kimberly F. , Pugh, Elizabeth, Brott, Thomas G. , Brown, Robert D., Nalls, Michael A., Rich, Stephen S. , Worrall, Bradford B. , Anderson, Christopher D. , Biffi, Alessandro , Cortellini, Lynelle, Furie, Karen L., Rost, Natalia S. , Manolio, Teri A. , Kittner, Steven J. , Mitchell, Braxton D. , Cole, John W. , Stine, Oscar Colin , Nelson, Sarah C. , Ling, Hua , Meschia, James F. , Rosand, Jonathan M. , Rich, Stephen S , Mitchell, Braxton D
G3 Genes|Genomes|Genetics | December 14, 2011 | Volume: 1 | Issue: 6 | Pages: 505-514
Abstract Ischemic stroke (IS) is among the leading causes of death in Western countries. There is a significant genetic component to IS susceptibility, especially among young adults. To date, research to identify genetic loci predisposing to stroke has met only with limited success. We performed a genome-wide association (GWA) analysis of early-onset IS to identify potential stroke susceptibility loci. The GWA analysis was conducted by genotyping 1 million SNPs in a biracial population of 889 IS cases and 927 controls, ages 15–49 years. Genotypes were imputed using the HapMap3 reference panel to provide 1.4 million SNPs for analysis. Logistic regression models adjusting for age, recruitment stages, and population structure were used to determine the association of IS with individual SNPs. Although no single SNP reached genome-wide significance (P < 5 × 10−8), we identified two SNPs in chromosome 2q23.3, rs2304556 (in FMNL2; P = 1.2 × 10−7) and rs1986743 (in ARL6IP6; P = 2.7 × 10−7), strongly associated with early-onset stroke. These data suggest that a novel locus on human chromosome 2q23.3 may be associated with IS susceptibility among young adults.