Genetic architecture of band neutrophil fraction in Iceland

• Published in: Communications Biology
• Main Authors: Oskarsson, Gudjon R., Magnússon, Magnús Karl, Oddson, Ásmundur, Jensson, Brynjar O, Friðriksdóttir, Rún, Arnadottir, Gudny A, Katrinardottir, Hildigunnur, Rögnvaldsson, Sölvi, Halldórsson, Gísli Hreinn, Sveinbjörnsson, Gardar, Ivarsdottir, Erna V., Stefánsdóttir, Lilja, Ferkingstad, Egil, Norland, Kristjan, Tragante, Vinicius, Sæmundsdóttir, Jóna, Jónasdóttir, Áslaug, Jonasdottir, Adalbjorg, Sigurjonsdottir, Svanhvit, Petursdottir, Karen O., Davidsson, Olafur B, Rafnar, Thorunn, Hólm, Hilma, Ólafsson, Ísleifur, Önundarson, Páll Torfi, Viðarsson, Brynjar, Sigurdardottir, Olof G., Másson, Gísli, Gudbjartsson, Daniel Fannar, Jónsdóttir, Ingileif, Norddahl, Gudmundur L., Þorsteinsdóttir, Unnur, Sulem, Patrick, Stefánsson, Kári
• Other Authors: Faculty of Medicine, Faculty of Industrial Engineering, Mechanical Engineering and Computer Science, Health Sciences, Landspitali - The National University Hospital of Iceland
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2022
• Subjects: Lífefna- og sameindalíffræði; Blóðlæknisfræði; Náttúrufræðingar; Genome-Wide Association Study; Granulocytes / metabolism; Humans; Iceland; Neutrophils / metabolism; Pelger-Huet Anomaly* / genetics; Neutrophils/metabolism; Pelger-Huet Anomaly/genetics; Granulocytes/metabolism; General Agricultural and Biological Sciences; General Biochemistry,Genetics and Molecular Biology; Medicine (miscellaneous); Huet
• Online Access: https://hdl.handle.net/20.500.11815/3478; https://doi.org/10.1038/s42003-022-03462-1

© 2022. The Author(s). The characteristic lobulated nuclear morphology of granulocytes is partially determined by composition of nuclear envelope proteins. Abnormal nuclear morphology is primarily observed as an increased number of hypolobulated immature neutrophils, called band cells, during infection or in rare envelopathies like Pelger-Huët anomaly. To search for sequence variants affecting nuclear morphology of granulocytes, we performed a genome-wide association study using band neutrophil fraction from 88,101 Icelanders. We describe 13 sequence variants affecting band neutrophil fraction at nine loci. Five of the variants are at the Lamin B receptor (LBR) locus, encoding an inner nuclear membrane protein. Mutations in LBR are linked to Pelger-Huët anomaly. In addition, we identify cosegregation of a rare stop-gain sequence variant in LBR and Pelger Huët anomaly in an Icelandic eight generation pedigree, initially reported in 1963. Two of the other loci include genes which, like LBR, play a role in the nuclear membrane function and integrity. These GWAS results highlight the role proteins of the inner nuclear membrane have as important for neutrophil nuclear morphology. Peer reviewed