Genetic analysis of over half a million people characterises C-reactive protein loci

Saredo Said; Raha Pazoki; Ville Karhunen; Urmo Võsa; Symen Ligthart; Barbara Bodinier; Fotios Koskeridis; Paul Welsh; Behrooz Z Alizadeh; Daniel I Chasman; Naveed Sattar; Marc Chadeau-Hyam; Evangelos Evangelou; Marjo-Riitta Jarvelin; Paul Elliott; Ioanna Tzoulaki; Abbas Dehghan

doi:10.1038/s41467-022-29650-5

Genetic analysis of over half a million people characterises C-reactive protein loci

Saredo Said, Raha Pazoki, Ville Karhunen, Urmo Võsa, Symen Ligthart, Barbara Bodinier, Fotios Koskeridis, Paul Welsh, Behrooz Z Alizadeh, Daniel I Chasman, Naveed Sattar, Marc Chadeau-Hyam, Evangelos Evangelou, Marjo-Riitta Jarvelin, Paul Elliott, Ioanna Tzoulaki, Abbas Dehghan^*

^*Corresponding author voor dit werk

Onderzoeksoutput: Article › Academic › peer review

73 Citaten (Scopus)

66 Downloads (Pure)

Samenvatting

Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein (CRP), a marker of systemic inflammation, in UK Biobank participants (N = 427,367, European descent) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (total N = 575,531 European descent). We identify 266 independent loci, of which 211 are not previously reported. Gene-set analysis highlighted 42 gene sets associated with CRP levels (p ≤ 3.2 ×10-6) and tissue expression analysis indicated a strong association of CRP related genes with liver and whole blood gene expression. Phenome-wide association study identified 27 clinical outcomes associated with genetically determined CRP and subsequent Mendelian randomisation analyses supported a causal association with schizophrenia, chronic airway obstruction and prostate cancer. Our findings identified genetic loci and functional properties of chronic low-grade inflammation and provided evidence for causal associations with a range of diseases.

Originele taal-2	English
Artikelnummer	2198
Aantal pagina's	10
Tijdschrift	Nature Communications
Volume	13
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1038/s41467-022-29650-5
Status	Published - 22-apr.-2022

Toegang tot document

10.1038/s41467-022-29650-5Licentie: CC BY

Genetic analysis of over half a million people characterises C-reactive protein lociFinal publisher's version, 1,54 MBLicentie: CC BY

Handle.net

Permanente koppeling

Citeer dit

Said, S., Pazoki, R., Karhunen, V., Võsa, U., Ligthart, S., Bodinier, B., Koskeridis, F., Welsh, P., Alizadeh, B. Z., Chasman, D. I., Sattar, N., Chadeau-Hyam, M., Evangelou, E., Jarvelin, M.-R., Elliott, P., Tzoulaki, I., & Dehghan, A. (2022). Genetic analysis of over half a million people characterises C-reactive protein loci. Nature Communications, 13(1), Artikel 2198. https://doi.org/10.1038/s41467-022-29650-5

@article{7e1c29a8e7ca4c36a59409b127d1d9f0,

title = "Genetic analysis of over half a million people characterises C-reactive protein loci",

abstract = "Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein (CRP), a marker of systemic inflammation, in UK Biobank participants (N = 427,367, European descent) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (total N = 575,531 European descent). We identify 266 independent loci, of which 211 are not previously reported. Gene-set analysis highlighted 42 gene sets associated with CRP levels (p ≤ 3.2 ×10-6) and tissue expression analysis indicated a strong association of CRP related genes with liver and whole blood gene expression. Phenome-wide association study identified 27 clinical outcomes associated with genetically determined CRP and subsequent Mendelian randomisation analyses supported a causal association with schizophrenia, chronic airway obstruction and prostate cancer. Our findings identified genetic loci and functional properties of chronic low-grade inflammation and provided evidence for causal associations with a range of diseases.",

keywords = "C-Reactive Protein/genetics, Genetic Loci, Genome-Wide Association Study, Humans, Inflammation/genetics, Male, Mendelian Randomization Analysis, Phenomics, Polymorphism, Single Nucleotide",

author = "Saredo Said and Raha Pazoki and Ville Karhunen and Urmo V{\~o}sa and Symen Ligthart and Barbara Bodinier and Fotios Koskeridis and Paul Welsh and Alizadeh, {Behrooz Z} and Chasman, {Daniel I} and Naveed Sattar and Marc Chadeau-Hyam and Evangelos Evangelou and Marjo-Riitta Jarvelin and Paul Elliott and Ioanna Tzoulaki and Abbas Dehghan",

note = "{\textcopyright} 2022. The Author(s).",

year = "2022",

month = apr,

day = "22",

doi = "10.1038/s41467-022-29650-5",

language = "English",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Said, S, Pazoki, R, Karhunen, V, Võsa, U, Ligthart, S, Bodinier, B, Koskeridis, F, Welsh, P, Alizadeh, BZ, Chasman, DI, Sattar, N, Chadeau-Hyam, M, Evangelou, E, Jarvelin, M-R, Elliott, P, Tzoulaki, I & Dehghan, A 2022, 'Genetic analysis of over half a million people characterises C-reactive protein loci', Nature Communications, vol. 13, nr. 1, 2198. https://doi.org/10.1038/s41467-022-29650-5

TY - JOUR

T1 - Genetic analysis of over half a million people characterises C-reactive protein loci

AU - Said, Saredo

AU - Pazoki, Raha

AU - Karhunen, Ville

AU - Võsa, Urmo

AU - Ligthart, Symen

AU - Bodinier, Barbara

AU - Koskeridis, Fotios

AU - Welsh, Paul

AU - Alizadeh, Behrooz Z

AU - Chasman, Daniel I

AU - Sattar, Naveed

AU - Chadeau-Hyam, Marc

AU - Evangelou, Evangelos

AU - Jarvelin, Marjo-Riitta

AU - Elliott, Paul

AU - Tzoulaki, Ioanna

AU - Dehghan, Abbas

PY - 2022/4/22

Y1 - 2022/4/22

N2 - Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein (CRP), a marker of systemic inflammation, in UK Biobank participants (N = 427,367, European descent) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (total N = 575,531 European descent). We identify 266 independent loci, of which 211 are not previously reported. Gene-set analysis highlighted 42 gene sets associated with CRP levels (p ≤ 3.2 ×10-6) and tissue expression analysis indicated a strong association of CRP related genes with liver and whole blood gene expression. Phenome-wide association study identified 27 clinical outcomes associated with genetically determined CRP and subsequent Mendelian randomisation analyses supported a causal association with schizophrenia, chronic airway obstruction and prostate cancer. Our findings identified genetic loci and functional properties of chronic low-grade inflammation and provided evidence for causal associations with a range of diseases.

AB - Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein (CRP), a marker of systemic inflammation, in UK Biobank participants (N = 427,367, European descent) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (total N = 575,531 European descent). We identify 266 independent loci, of which 211 are not previously reported. Gene-set analysis highlighted 42 gene sets associated with CRP levels (p ≤ 3.2 ×10-6) and tissue expression analysis indicated a strong association of CRP related genes with liver and whole blood gene expression. Phenome-wide association study identified 27 clinical outcomes associated with genetically determined CRP and subsequent Mendelian randomisation analyses supported a causal association with schizophrenia, chronic airway obstruction and prostate cancer. Our findings identified genetic loci and functional properties of chronic low-grade inflammation and provided evidence for causal associations with a range of diseases.

KW - C-Reactive Protein/genetics

KW - Genetic Loci

KW - Genome-Wide Association Study

KW - Humans

KW - Inflammation/genetics

KW - Male

KW - Mendelian Randomization Analysis

KW - Phenomics

KW - Polymorphism, Single Nucleotide

U2 - 10.1038/s41467-022-29650-5

DO - 10.1038/s41467-022-29650-5

M3 - Article

C2 - 35459240

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2198

ER -

Genetic analysis of over half a million people characterises C-reactive protein loci

Samenvatting

Toegang tot document

Handle.net

Vingerafdruk

Citeer dit