Anemia, Sickle Cell study with SNP/CNV Genotypes (NGS) data on dbGaP (327 participants)

phs002470 — A Polygenic Score for Acute Vaso-Occlusive Pain in Pediatric Sickle Cell    Disease

Recurrent acute pain, or vaso-occlusive pain crisis (VOP), is the most common complication of sickle cell disease and correlates strongly with increased hospital visits and early mortality (PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/1710777">1710777</a>). While the genetics of VOP in sickle cell patients has been studied (PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/29205277">29205277</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/27883292">27883292</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/25102390">25102390</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/30079801">30079801</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/22925497">22925497</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/29531649">29531649</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/29620434">29620434</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/19468207">19468207</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/20172753">20172753</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/22576309">22576309</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/30031848">30031848</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/24136375">24136375</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/27603703">27603703</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/29559808">29559808</a>), it is not fully understood. Using whole genome sequencing, we interrogated the α-thalassemia deletion -α3.7 and 133 candidate single-nucleotide polymorphisms (SNPs) across 66 genes for associations with VOP in 327 SCCRIP participants followed longitudinally over 6 years. Twenty-one SNPs in 9 loci were associated with VOP, including 3 (BCL11A, MYB, and the β-like globin gene cluster) that regulate erythrocyte fetal hemoglobin (HbF) levels and 6 (COMT, TBC1D1, KCNJ6, FAAH, NR3C1, and IL1A) that were associated previously with various pain syndromes. An unweighted PGS integrating all 21 SNPs was associated with the VOP event rate (estimate, 0.35; standard error, 0.04; P = 5.9 × 10−14) and VOP event occurrence (estimate, 0.42; standard error, 0.06; P = 4.1 × 10−13). These associations were stronger than those of any single locus. Our findings provide insights into the genetic modulation of VOP in children with SCD. More generally, we demonstrate the utility of WGS for investigating genetic contributions to the variable expression of SCD-associated morbidities.For publications, written, and/or oral presentations resulting from use of this data, please cite the following information: "The original data description for A Polygenic Score for Acute Vaso-Occlusive Pain in Pediatric Sickle Cell Disease can be found here: (Journal Citation Blood Adv. 2021 Jul 27;5(14):2839-2851) (PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/34283174/">34283174</a>)."