Genome-wide association study identifies 16 genomic regions associated with circulating cytokines at birth

English version

Autoři: Yunpeng Wang ^aff001; Ron Nudel ^aff001; Michael E. Benros ^aff001; Kristin Skogstrand ^aff001; Simon Fishilevich ^aff008; ; Doron Lancet ^aff008; Jiangming Sun ^aff001; David M. Hougaard ^aff001; Ole A. Andreassen ^aff003; Preben Bo Mortensen ^aff001; Alfonso Buil ^aff001; Thomas F. Hansen ^aff001; Wesley K. Thompson ^aff001; Thomas Werge ^aff001
Působiště autorů: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark ^aff001; Institute of Biological Psychiatry, Mental Health Center St. Hans, Mental Health Services Copenhagen, Denmark ^aff002; Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, and Oslo University Hospital, Norway ^aff003; Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo, Norway ^aff004; Mental Health Center Copenhagen, Copenhagen University Hospital, Denmark ^aff005; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark ^aff006; Danish Centre for Neonatal Screening, Department of Congenital Diseases, Statens Serum Institut, Denmark ^aff007; Department of Molecular Genetics, Weizmann Institute of Science, Israel ^aff008; Department of Economics and Business Economics-National Centre for Register-based Research, University of Aarhus, Denmark ^aff009; Danish Headache Center, Department of Neurology, University Hospital Copenhagen, Denmark ^aff010; Division of Biostatistics, Department of Family Medicine and Public Health, University of California, San Diego, California, United States of America ^aff011; Department of Clinical Medicine, University of Copenhagen, Denmark ^aff012
Vyšlo v časopise: Genome-wide association study identifies 16 genomic regions associated with circulating cytokines at birth. PLoS Genet 16(11): e1009163. doi:10.1371/journal.pgen.1009163
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009163

Souhrn

Circulating inflammatory markers are essential to human health and disease, and they are often dysregulated or malfunctioning in cancers as well as in cardiovascular, metabolic, immunologic and neuropsychiatric disorders. However, the genetic contribution to the physiological variation of levels of circulating inflammatory markers is largely unknown. Here we report the results of a genome-wide genetic study of blood concentration of ten cytokines, including the hitherto unexplored calcium-binding protein (S100B). The study leverages a unique sample of neonatal blood spots from 9,459 Danish subjects from the iPSYCH initiative. We estimate the SNP-heritability of marker levels as ranging from essentially zero for Erythropoietin (EPO) up to 73% for S100B. We identify and replicate 16 associated genomic regions (p < 5 x 10⁻⁹), of which four are novel. We show that the associated variants map to enhancer elements, suggesting a possible transcriptional effect of genomic variants on the cytokine levels. The identification of the genetic architecture underlying the basic levels of cytokines is likely to prompt studies investigating the relationship between cytokines and complex disease. Our results also suggest that the genetic architecture of cytokines is stable from neonatal to adult life.

Klíčová slova:

Cytokines – Gene regulation – Genetics of disease – Genome annotation – Genomics – Inflammation – Inflammatory diseases – Single nucleotide polymorphisms

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