A locus on chromosome 5 shows African ancestry–limited association with alloimmunization in sickle cell disease by Lesedi M. Williams, Zhihua Qi, Ken Batai, Stanley Hooker, Nancy J. Hall, Roberto F. Machado, Alice Chen, Sally Campbell-Lee, Yongtao Guan, Rick Kittles, and Neil A. Hanchard BloodAdv Volume 2(24):3637-3647 December 26, 2018 ©2018 by American Society of Hematology

Lesedi M. Williams et al. Blood Adv 2018;2:3637-3647 ©2018 by American Society of Hematology

Allelic association with responder status. Allelic association with responder status. (A) Loci on chromosomes 2 and 5 have SNPs close to genome-wide significance (red line, P = 5.0 × 10−8). Genomic inflation factor (based on median χ2) is 1.013. (B) LocusZoom plot of imputed chromosome 2 region. SNP rs66516066 reaches genome-wide significance. A SNP cluster in strong LD is 0.5 Mb downstream of NBAS. (C) LocusZoom plot of imputed chromosome 5 region. rs7585387 SNP cluster is located with long noncoding RNA gene LOC101927766 and 0.7 Mb upstream of ADRA1B. Purple highlighted region between peaks of increase recombination rate indicates the location of identified rare haplotype. Lesedi M. Williams et al. Blood Adv 2018;2:3637-3647 ©2018 by American Society of Hematology

Chromosome 5 regulatory locus. Chromosome 5 regulatory locus. Screenshot from the University of California, Santa Cruz, Genome browser80 (http://genome.ucsc.edu; Human Genome Build GRCh37/hg37 released in February 2009) showing regional binding sites for multiple transcription factors and enhancer binding proteins. Location of SNP rs75853687 is indicated by the light blue highlight. SNP rs75853687 within 1 base pair of the CEBPB binding motif, 5′-T[TG]NNGNAA[TG]-3′. Lesedi M. Williams et al. Blood Adv 2018;2:3637-3647 ©2018 by American Society of Hematology

Local African ancestry of responders and nonresponders. Local African ancestry of responders and nonresponders. (A) Local ancestry across chromosome 11 in cases and controls shows a strong peak of African ancestry at the HBB locus. (B-C) local African ancestry on chromosomes 2 and 5 in responders (cases) and nonresponders (controls). At each locus mean values are plotted as a bold line, with shaded values indicating upper (95%) and lower (5%) CIs. Lesedi M. Williams et al. Blood Adv 2018;2:3637-3647 ©2018 by American Society of Hematology

Ancestry-restricted haplotype association at chromosome 5 candidate locus. Ancestry-restricted haplotype association at chromosome 5 candidate locus. SNP rs75853687 shows significant association (log10 BF= 4.954) in the restricted African ancestry analysis (A) that is not detected in the restricted European ancestry analysis (B). Red lines show typical threshold for significant log10 BF. Lesedi M. Williams et al. Blood Adv 2018;2:3637-3647 ©2018 by American Society of Hematology