Assessing the effect of rare sequence variants in genome-wide association studies of quantitative hematological traits

BMC Seminar Thursday 15 April, 12:00

Speaker: Guðjón Reykdal Óskarsson, doctoral student at DeCODE genetics

Title: Assessing the effect of rare sequence variants in genome-wide association studies of quantitative hematological traits

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Abstract: Mutations leading to severe phenotypes or having large effects on quantitative traits are more likely to be rare due to negative selection. Also, sequence variants with large phenotypic effect sizes are enriched within a coding sequence of the genome. Studying these rare sequence variants therefore increases the probability of finding variants that give insight in to physiology and pathways involved in the functional role of a gene on a disease or traits.

In my studies we are able to identify and test association to rare sequence variants (minor allele frequency of 1-0.01%) in genome-wide association studies. In Iceland, we used a learning set based on whole-genome sequencing of a large fraction (~15%) of the nation followed by imputation on a set containing close to 50% of this population This increased the likelihood of finding, imputing and testing rare sequence variants. In addition to having a large genetic set, it is also important to have a large phenotype data to associate the variants with a phenotype. Therefore, to assess the effect of rare sequence variants, I studied quantitative hematological traits. Quantitative hematological traits are routinely measured in the medical context and a large fraction of Icelanders have available blood measurements.

In this talk I will go through results of my doctoral studies at DeCODE genetics, with focus on quantitative hematological traits. The three studies I will talk about are meta-analysis of genome-wide association studies of hemoglobin concentration (PMID: 32327693), genome-wide association study of serum erythropoieitin in Iceland (PMID: 30271932),  and unpublished results ready for submission of a genome-wide association study of neutrophil nuclear morphology in Iceland.