Recurrent acute pain, or vaso-occlusive pain crisis (VOC), is the most common complication of sickle cell disease and correlates strongly with increased hospital visits and early mortality. However, potential genetic contributions to frequent or recurrent episodes of VOC in sickle cell patients are poorly understood.

In previous work [PMID: 28584135], a genome-wide association study identified an association between acute pain episodes and the KIAA1109-TENR-IL2-IL21 region on chromosome 4. To gain further insights into this association, we investigated this region using whole genome sequencing and identified new risk variants associated with shorter time to first pain event. These variants likely contribute to the regulation of IL2, an inflammatory marker. In the future, screening for these variants may help identify individuals who require more careful monitoring and who may be candidates for research studies aimed at reducing pain episodes in individuals with sickle cell disease.

Genetics of Hematological Indices
Variants and Phenotypes

Explore the relationship of phenotypes, such as blood count values, with specific genotypes, such as deletional alpha- and beta-thalassemia status and relevant single nucleotide variants. As an example, this tool may be used to view relationships between mean corpuscular volume (MCV) and alpha- and beta-thalassemia status.

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Genome Browser
Genome Browser

View single nucleotide variants and small indels that have been annotated with pain data. Variants within the KIAA1109-TENR-IL2-IL21 locus have been analyzed for genetic association with pain rate and time to first pain event within our sickle cell disease cohort. Tracks within the browser, which can be selected from the "Tracks" menu, include the pain rate and time to first VOC event p-values, average pain rate by genotype, and average fetal hemoglobin by genotype.

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Association of Genetic Variants with Age of First Vaso-Occlusive Crisis

Kaplan-Meier curves showing that different genotypes of the four variants within the KIAA1109-TENR-IL2-IL21 locus can stratify the age of first VOC within our sickle cell cohort.