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

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  • Yunpeng Wang, Mental Health Services Copenhagen, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, University of Oslo
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  • Ron Nudel, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Mental Health Services Copenhagen
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  • Michael E Benros, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Københavns Universitet
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  • Kristin Skogstrand, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Statens Serum Institut
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  • Simon Fishilevich, Weizmann Inst Sci, Weizmann Institute of Science, Dept Biomol Sci
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  • iPSYCH-BROAD
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  • Doron Lancet, Weizmann Inst Sci, Weizmann Institute of Science, Dept Biomol Sci
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  • Jiangming Sun, Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Mental Health Services Copenhagen
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  • David M Hougaard, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Statens Serum Institut
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  • Ole A Andreassen, University of Oslo
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  • Preben Bo Mortensen
  • Alfonso Buil, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Mental Health Services Copenhagen
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  • Thomas F Hansen, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Mental Health Services Copenhagen, Københavns Universitet
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  • Wesley K Thompson, Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Mental Health Services Copenhagen, University of California
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  • Thomas Werge, Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Mental Health Services Copenhagen, Københavns Universitet

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.

OriginalsprogEngelsk
Artikelnummere1009163
TidsskriftPLOS Genetics
Vol/bind16
Nummer11
ISSN1553-7390
DOI
StatusUdgivet - nov. 2020

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