{"entity": "publication", "iuid": "23ed7542420348a2ad0dc84ea88454d3", "timestamp": "2026-08-17T08:07:52.668Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/23ed7542420348a2ad0dc84ea88454d3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/23ed7542420348a2ad0dc84ea88454d3"}}, "title": "A genome-wide association study of IgM antibody against phosphorylcholine: shared genetics and phenotypic relationship to chronic lymphocytic leukemia.", "authors": [{"family": "Chen", "given": "Xu", "initials": "X"}, {"family": "Gustafsson", "given": "Stefan", "initials": "S"}, {"family": "Whitington", "given": "Thomas", "initials": "T"}, {"family": "Born\u00e9", "given": "Yan", "initials": "Y"}, {"family": "Lorentzen", "given": "Erik", "initials": "E"}, {"family": "Sun", "given": "Jitong", "initials": "J"}, {"family": "Almgren", "given": "Peter", "initials": "P"}, {"family": "Su", "given": "Jun", "initials": "J"}, {"family": "Karlsson", "given": "Robert", "initials": "R"}, {"family": "Song", "given": "Jie", "initials": "J"}, {"family": "Lu", "given": "Yi", "initials": "Y"}, {"family": "Zhan", "given": "Yiqiang", "initials": "Y"}, {"family": "H\u00e4gg", "given": "Sara", "initials": "S"}, {"family": "Svensson", "given": "Per", "initials": "P"}, {"family": "Smedby", "given": "Karin E", "initials": "KE"}, {"family": "Slager", "given": "Susan L", "initials": "SL"}, {"family": "Ingelsson", "given": "Erik", "initials": "E"}, {"family": "Lindgren", "given": "Cecilia M", "initials": "CM"}, {"family": "Morris", "given": "Andrew P", "initials": "AP"}, {"family": "Melander", "given": "Olle", "initials": "O"}, {"family": "Karlsson", "given": "Thomas", "initials": "T"}, {"family": "de Faire", "given": "Ulf", "initials": "U"}, {"family": "Caidahl", "given": "Kenneth", "initials": "K"}, {"family": "Engstr\u00f6m", "given": "Gunnar", "initials": "G"}, {"family": "Lind", "given": "Lars", "initials": "L"}, {"family": "Karlsson", "given": "Mikael C I", "initials": "MCI"}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "Frosteg\u00e5rd", "given": "Johan", "initials": "J"}, {"family": "Magnusson", "given": "Patrik K E", "initials": "PKE"}], "type": "journal article", "published": "2018-05-15", "journal": {"volume": "27", "issn": "1460-2083", "issue": "10", "pages": "1809-1818", "title": "Hum. Mol. Genet.", "issn-l": "0964-6906"}, "abstract": "Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWASs) in four European-ancestry cohorts, six single nucleotide polymorphisms (SNPs) in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined \u03b2\u2009=\u20090.19, 95% confidence interval 0.13-0.24, P\u2009=\u20094.3\u2009\u00d7\u200910-11). The haplotype tagged by rs35923643-G (or its proxy SNP rs735665-A) is also known as the top risk allele for chronic lymphocytic leukemia (CLL), and a main increasing allele for general IgM. By using summary GWAS results of IgM anti-PC and CLL in the polygenic risk score (PRS) analysis, PRS on the basis of IgM anti-PC risk alleles positively associated with CLL risk (explained 0.6% of CLL variance, P\u2009=\u20091.2\u2009\u00d7\u200910-15). Functional prediction suggested that rs35923643-G might impede the binding of Runt-related transcription factor 3, a tumor suppressor playing a central role in the immune regulation of cancers. Contrary to the expectations from the shared genetics between IgM anti-PC and CLL, an inverse relationship at the phenotypic level was found in a nested case-control study (30 CLL cases with 90 age- and sex-matched controls), potentially reflecting reverse causation. The suggested function of the top variant as well as the phenotypic association between IgM anti-PC and CLL risk needs replication and motivates further studies.", "doi": "10.1093/hmg/ddy094", "pmid": "29547969", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "4935077"}], "notes": [], "created": "2018-05-25T13:25:50.026Z", "modified": "2024-01-16T13:48:46.299Z"}