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