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Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders
- Source :
- Am J Hum Genet, Pool, R, de Geus, E, Hottenga, J J, Willemsen, G, Boomsma, D I, LifeLines Cohort Study & CHARGE Inflammation Working Group 2018, ' Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders ', American Journal of Human Genetics, vol. 103, no. 5, pp. 691-706 . https://doi.org/10.1016/j.ajhg.2018.09.009, American Journal of Human Genetics, American Journal of Human Genetics, 2018, 103 (5), pp.691-706. ⟨10.1016/j.ajhg.2018.09.009⟩, The American Journal of Human Genetics, American journal of human genetics, 103(5), 691-706. Cell Press, American Journal of Human Genetics, 103(5), 691-706. Cell Press, American Journal of Human Genetics, 103(5), 691-706. CELL PRESS, American journal of human genetics 103 (2018): 691–706. doi:10.1016/j.ajhg.2018.09.009, info:cnr-pdr/source/autori:Ligthart S.; Vaez A.; Vosa U.; Stathopoulou M.G.; de Vries P.S.; Prins B.P.; Van der Most P.J.; Tanaka T.; Naderi E.; Rose L.M.; Wu Y.; Karlsson R.; Barbalic M.; Lin H.; Pool R.; Zhu G.; Mace A.; Sidore C.; Trompet S.; Mangino M.; Sabater-Lleal M.; Kemp J.P.; Abbasi A.; Kacprowski T.; Verweij N.; Smith A.V.; Huang T.; Marzi C.; Feitosa M.F.; Lohman K.K.; Kleber M.E.; Milaneschi Y.; Mueller C.; Huq M.; Vlachopoulou E.; Lyytikainen L.-P.; Oldmeadow C.; Deelen J.; Perola M.; Zhao J.H.; Feenstra B.; Alizadeh B.Z.; Boezen H.M.; Franke L.; van der Harst P.; Navis G.; Rots M.; Snieder H.; Swertz M.; Wolffenbuttel B.H.R.; Wijmenga C.; Amini M.; Benjamin E.; Chasman D.I.; Dehghan A.; Ahluwalia T.S.; Meigs J.; Tracy R.; Alizadeh B.Z.; Ligthart S.; Bis J.; Eiriksdottir G.; Pankratz N.; Gross M.; Rainer A.; Snieder H.; Wilson J.G.; Psaty B.M.; Dupuis J.; Prins B.; Vaso U.; Stathopoulou M.; Franke L.; Lehtimaki T.; Koenig W.; Jamshidi Y.; Siest S.; Abbasi A.; Uitterlinden A.G.; Abdollahi M.; Schnabel R.; Schick U.M.; Nolte I.M.; Kraja A.; Hsu Y.-H.; Tylee D.S.; Zwicker A.; Uher R.; Davey-Smith G.; Morrison A.C.; Hicks A.; van Duijn C.M.; Ward-Caviness C.; Boerwinkle E.; Rotter J.; Rice K.; Lange L.; Perola M.; de Geus E.; Morris A.P.; Makela K.M.; Stacey D.; Eriksson J.; Frayling T.M.; Slagboom E.P.; Lahti J.; Schraut K.E.; Fornage M.; Suktitipat B.; Chen W.-M.; Li X.; Nutile T.; Malerba G.; Luan J.; Bak T.; Schork N.; Del Greco M. F.; Thiering E.; Mahajan A.; Marioni R.E.; Mihailov E.; Eriksson J.; Ozel A.B.; Zhang W.; Nethander M.; Cheng Y.-C.; Aslibekyan S.; Ang W.; Gandin I.; Yengo L.; Portas L.; Kooperberg C.; Hofer E.; Rajan K.B.; Schurmann C.; den Hollander W.; Ahluwalia T.S.; Zhao J.; Draisma H.H.M.; Ford I.; Timpson N.; Teumer A.; Huang H.; Wahl S.; Liu Y.; Huang J.; Uh H.-W.; Geller F.; Joshi P.K.; Yanek L.R.; Trabetti E.; Lehne B.; Vozzi D.; Verbanck M.; Biino G.; Saba Y.; Meulenbelt I.; O'Connell J.R.; Laakso M.; Giulianini F.; Magnusson P.K.E.; Ballantyne C.M.; Hottenga J.J.; Montgomery G.W.; Rivadineira F.; Rueedi R.; Steri M.; Herzig K.-H.; Stott D.J.; Menni C.; Franberg M.; St. Pourcain B.; Felix S.B.; Pers T.H.; Bakker S.J.L.; Kraft P.; Peters A.; Vaidya D.; Delgado G.; Smit J.H.; Grossmann V.; Sinisalo J.; Seppala I.; Williams S.R.; Holliday E.G.; Moed M.; Langenberg C.; Raikkonen K.; Ding J.; Campbell H.; Sale M.M.; Chen Y.-D.I.; James A.L.; Ruggiero D.; Soranzo N.; Hartman C.A.; Smith E.N.; Berenson G.S.; Fuchsberger C.; Hernandez D.; Tiesler C.M.T.; Giedraitis V.; Liewald D.; Fischer K.; Mellstrom D.; Larsson A.; Wang Y.; Scott W.R.; Lorentzon M.; Beilby J.; Ryan K.A.; Pennell C.E.; Vuckovic D.; Balkau B.; Concas M.P.; Schmidt R.; Mendes de Leon C.F.; Bottinger E.P.; Kloppenburg M.; Paternoster L.; Boehnke M.; Musk A.W.; Willemsen G.; Evans D.M.; Madden P.A.F.; Kahonen M.; Kutalik Z.; Zoledziewska M.; Karhunen V.; Kritchevsky S.B.; Sattar N.; Lachance G.; Clarke R.; Harris T.B.; Raitakari O.T.; Attia J.R.; van Heemst D.; Kajantie E.; Sorice R.; Gambaro G.; Scott R.A.; Hicks A.A.; Ferrucci L.; Standl M.; Lindgren C.M.; Starr J.M.; Karlsson M.; Lind L.; Li J.Z.; Chambers J.C.; Mori T.A.; de Geus E.J.C.N.; Heath A.C.; Martin N.G.; Auvinen J.; Buckley B.M.; de Craen A.J.M.; Waldenberger M.; Strauch K.; Meitinger T.; Scott R.J.; McEvoy M.; Beekman M.; Bombieri C.; Ridker P.M.; Mohlke K.L.; Pedersen N.L.; Morrison A.C.; Boomsma D.I.; Whitfield J.B.; Strachan D.P.; Hofman A.; Vollenweider P.; Cucca F.; Jarvelin M.-R.; Jukema J.W.; Spector T.D.; Hamsten A.; Zeller T.; Uitterlinden A.G.; Nauck M.; Gudnason V.; Qi L.; Grallert H.; Borecki I.B.; Rotter J.I.; Marz W.; Wild P.S.; Lokki M.-L.; Boyle M.; Salomaa V.; Melbye M.; Eriksson J.G.; Wilson J.F.; Penninx B.W.J.H.; Becker D.M.; Worrall B.B.; Gibson G.; Krauss R.M.; Ciullo M.; Zaza G.; Wareham N.J.; Oldehinkel A.J.; Palmer L.J.; Murray S.S.; Pramstaller P.P.; Bandinelli S.; Heinrich J.; Ingelsson E.; Deary I.J.; Magi R.; Vandenput L.; van der Harst P.; Desch K.C.; Kooner J.S.; Ohlsson C.; Hayward C.; Lehtimaki T.; Shuldiner A.R.; Arnett D.K.; Beilin L.J.; Robino A.; Froguel P.; Pirastu M.; Jess T.; Koenig W.; Loos R.J.F.; Evans D.A.; Schmidt H.; Smith G.D.; Slagboom P.E.; Eiriksdottir G.; Morris A.P.; Psaty B.M.; Tracy R.P.; Nolte I.M.; Boerwinkle E.; Visvikis-Siest S.; Reiner A.P.; Gross M.; Bis J.C.; Franke L.; Franco O.H.; Benjamin E.J.; Chasman D.I.; Dupuis J.; Snieder H.; Dehghan A.; Alizadeh B.Z./titolo:Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders/doi:10.1016%2Fj.ajhg.2018.09.009/rivista:American journal of human genetics/anno:2018/pagina_da:691/pagina_a:706/intervallo_pagine:691–706/volume:103, Ligthart, S, Vaez, A, Võsa, U, Stathopoulou, M G, de Vries, P S, Prins, B P, Van der Most, P J, Tanaka, T, Naderi, E, Rose, L M, Wu, Y, Karlsson, R, Barbalic, M, Lin, H, Pool, R, Zhu, G, Macé, A, Sidore, C, Trompet, S, Mangino, M, Sabater-Lleal, M, Kemp, J P, Abbasi, A, Kacprowski, T, Verweij, N, Smith, A V, Huang, T, Marzi, C, Feitosa, M F, Lohman, K K, Kleber, M E, Milaneschi, Y, Mueller, C, Huq, M, Vlachopoulou, E, Lyytikäinen, L P, Oldmeadow, C, Deelen, J, Perola, M, Zhao, J, Davey-Smith, G, Hicks, A, Timpson, N, St. Pourcain, B, Soranzo, N, Paternoster, L, Evans, D M & Hicks, A & Palmer, L J & Davey-Smith, G 2018, ' Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders ', American Journal of Human Genetics, vol. 103, no. 5, pp. 691-706 . https://doi.org/10.1016/j.ajhg.2018.09.009, American Journal of Human Genetics, 103(5), 691-706, AMERICAN JOURNAL OF HUMAN GENETICS, American Journal of Human Genetics, Elsevier (Cell Press), 2018, 103 (5), pp.691-706. ⟨10.1016/j.ajhg.2018.09.009⟩, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, Lifelines Cohort Study 2018, ' Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders ', American journal of human genetics, vol. 103, no. 5, pp. 691-706 . https://doi.org/10.1016/j.ajhg.2018.09.009
- Publication Year :
- 2018
-
Abstract
- International audience; C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.Copyright © 2018 American Society of Human Genetics. All rights reserved.
- Subjects :
- 0301 basic medicine
Male
Netherlands Twin Register (NTR)
Bipolar Disorder
LD SCORE REGRESSION
[SDV]Life Sciences [q-bio]
Genome-wide association study
[SDV.GEN] Life Sciences [q-bio]/Genetics
Body Mass Index
inflammatory disorder
80 and over
WIDE ASSOCIATION
EPIDEMIOLOGY
ta318
International HapMap Project
Child
Genetics (clinical)
2. Zero hunger
Genetics
Genetics & Heredity
Aged, 80 and over
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
C-reactive proteingenome-wide association studyinflammationMendelian randomizationinflammatory disordersDEPICTcoronary artery diseaseschizophreniasystem biology
system biology
DEPICT
Mendelian Randomization Analysis
11 Medical And Health Sciences
Middle Aged
C-reactive protein
coronary artery disease
genome-wide association study
inflammation
inflammatory disorders
Mendelian randomization
schizophrenia
Adolescent
Adult
Aged
Biomarkers
C-Reactive Protein
Female
Genetic Loci
Genome-Wide Association Study
Humans
Inflammation
Liver
Metabolic Networks and Pathways
Schizophrenia
Young Adult
3. Good health
[SDV] Life Sciences [q-bio]
Medical genetics
Biomarker (medicine)
Life Sciences & Biomedicine
Human
medicine.medical_specialty
CHARGE Inflammation Working Group
Biology
IMMUNITY
ta3111
Article
03 medical and health sciences
SDG 3 - Good Health and Well-being
medicine
CORONARY-HEART-DISEASE
Mendelian Randomization Analysi
1000 Genomes Project
METAANALYSIS
Genetic association
[SDV.GEN]Life Sciences [q-bio]/Genetics
Science & Technology
ta1184
Metabolic Networks and Pathway
Biomarker
INSTRUMENTS
06 Biological Sciences
030104 developmental biology
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
LifeLines Cohort Study
Subjects
Details
- Language :
- English
- ISSN :
- 00029297 and 15376605
- Database :
- OpenAIRE
- Journal :
- Am J Hum Genet, Pool, R, de Geus, E, Hottenga, J J, Willemsen, G, Boomsma, D I, LifeLines Cohort Study & CHARGE Inflammation Working Group 2018, ' Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders ', American Journal of Human Genetics, vol. 103, no. 5, pp. 691-706 . https://doi.org/10.1016/j.ajhg.2018.09.009, American Journal of Human Genetics, American Journal of Human Genetics, 2018, 103 (5), pp.691-706. ⟨10.1016/j.ajhg.2018.09.009⟩, The American Journal of Human Genetics, American journal of human genetics, 103(5), 691-706. Cell Press, American Journal of Human Genetics, 103(5), 691-706. Cell Press, American Journal of Human Genetics, 103(5), 691-706. CELL PRESS, American journal of human genetics 103 (2018): 691–706. doi:10.1016/j.ajhg.2018.09.009, info:cnr-pdr/source/autori:Ligthart S.; Vaez A.; Vosa U.; Stathopoulou M.G.; de Vries P.S.; Prins B.P.; Van der Most P.J.; Tanaka T.; Naderi E.; Rose L.M.; Wu Y.; Karlsson R.; Barbalic M.; Lin H.; Pool R.; Zhu G.; Mace A.; Sidore C.; Trompet S.; Mangino M.; Sabater-Lleal M.; Kemp J.P.; Abbasi A.; Kacprowski T.; Verweij N.; Smith A.V.; Huang T.; Marzi C.; Feitosa M.F.; Lohman K.K.; Kleber M.E.; Milaneschi Y.; Mueller C.; Huq M.; Vlachopoulou E.; Lyytikainen L.-P.; Oldmeadow C.; Deelen J.; Perola M.; Zhao J.H.; Feenstra B.; Alizadeh B.Z.; Boezen H.M.; Franke L.; van der Harst P.; Navis G.; Rots M.; Snieder H.; Swertz M.; Wolffenbuttel B.H.R.; Wijmenga C.; Amini M.; Benjamin E.; Chasman D.I.; Dehghan A.; Ahluwalia T.S.; Meigs J.; Tracy R.; Alizadeh B.Z.; Ligthart S.; Bis J.; Eiriksdottir G.; Pankratz N.; Gross M.; Rainer A.; Snieder H.; Wilson J.G.; Psaty B.M.; Dupuis J.; Prins B.; Vaso U.; Stathopoulou M.; Franke L.; Lehtimaki T.; Koenig W.; Jamshidi Y.; Siest S.; Abbasi A.; Uitterlinden A.G.; Abdollahi M.; Schnabel R.; Schick U.M.; Nolte I.M.; Kraja A.; Hsu Y.-H.; Tylee D.S.; Zwicker A.; Uher R.; Davey-Smith G.; Morrison A.C.; Hicks A.; van Duijn C.M.; Ward-Caviness C.; Boerwinkle E.; Rotter J.; Rice K.; Lange L.; Perola M.; de Geus E.; Morris A.P.; Makela K.M.; Stacey D.; Eriksson J.; Frayling T.M.; Slagboom E.P.; Lahti J.; Schraut K.E.; Fornage M.; Suktitipat B.; Chen W.-M.; Li X.; Nutile T.; Malerba G.; Luan J.; Bak T.; Schork N.; Del Greco M. F.; Thiering E.; Mahajan A.; Marioni R.E.; Mihailov E.; Eriksson J.; Ozel A.B.; Zhang W.; Nethander M.; Cheng Y.-C.; Aslibekyan S.; Ang W.; Gandin I.; Yengo L.; Portas L.; Kooperberg C.; Hofer E.; Rajan K.B.; Schurmann C.; den Hollander W.; Ahluwalia T.S.; Zhao J.; Draisma H.H.M.; Ford I.; Timpson N.; Teumer A.; Huang H.; Wahl S.; Liu Y.; Huang J.; Uh H.-W.; Geller F.; Joshi P.K.; Yanek L.R.; Trabetti E.; Lehne B.; Vozzi D.; Verbanck M.; Biino G.; Saba Y.; Meulenbelt I.; O'Connell J.R.; Laakso M.; Giulianini F.; Magnusson P.K.E.; Ballantyne C.M.; Hottenga J.J.; Montgomery G.W.; Rivadineira F.; Rueedi R.; Steri M.; Herzig K.-H.; Stott D.J.; Menni C.; Franberg M.; St. Pourcain B.; Felix S.B.; Pers T.H.; Bakker S.J.L.; Kraft P.; Peters A.; Vaidya D.; Delgado G.; Smit J.H.; Grossmann V.; Sinisalo J.; Seppala I.; Williams S.R.; Holliday E.G.; Moed M.; Langenberg C.; Raikkonen K.; Ding J.; Campbell H.; Sale M.M.; Chen Y.-D.I.; James A.L.; Ruggiero D.; Soranzo N.; Hartman C.A.; Smith E.N.; Berenson G.S.; Fuchsberger C.; Hernandez D.; Tiesler C.M.T.; Giedraitis V.; Liewald D.; Fischer K.; Mellstrom D.; Larsson A.; Wang Y.; Scott W.R.; Lorentzon M.; Beilby J.; Ryan K.A.; Pennell C.E.; Vuckovic D.; Balkau B.; Concas M.P.; Schmidt R.; Mendes de Leon C.F.; Bottinger E.P.; Kloppenburg M.; Paternoster L.; Boehnke M.; Musk A.W.; Willemsen G.; Evans D.M.; Madden P.A.F.; Kahonen M.; Kutalik Z.; Zoledziewska M.; Karhunen V.; Kritchevsky S.B.; Sattar N.; Lachance G.; Clarke R.; Harris T.B.; Raitakari O.T.; Attia J.R.; van Heemst D.; Kajantie E.; Sorice R.; Gambaro G.; Scott R.A.; Hicks A.A.; Ferrucci L.; Standl M.; Lindgren C.M.; Starr J.M.; Karlsson M.; Lind L.; Li J.Z.; Chambers J.C.; Mori T.A.; de Geus E.J.C.N.; Heath A.C.; Martin N.G.; Auvinen J.; Buckley B.M.; de Craen A.J.M.; Waldenberger M.; Strauch K.; Meitinger T.; Scott R.J.; McEvoy M.; Beekman M.; Bombieri C.; Ridker P.M.; Mohlke K.L.; Pedersen N.L.; Morrison A.C.; Boomsma D.I.; Whitfield J.B.; Strachan D.P.; Hofman A.; Vollenweider P.; Cucca F.; Jarvelin M.-R.; Jukema J.W.; Spector T.D.; Hamsten A.; Zeller T.; Uitterlinden A.G.; Nauck M.; Gudnason V.; Qi L.; Grallert H.; Borecki I.B.; Rotter J.I.; Marz W.; Wild P.S.; Lokki M.-L.; Boyle M.; Salomaa V.; Melbye M.; Eriksson J.G.; Wilson J.F.; Penninx B.W.J.H.; Becker D.M.; Worrall B.B.; Gibson G.; Krauss R.M.; Ciullo M.; Zaza G.; Wareham N.J.; Oldehinkel A.J.; Palmer L.J.; Murray S.S.; Pramstaller P.P.; Bandinelli S.; Heinrich J.; Ingelsson E.; Deary I.J.; Magi R.; Vandenput L.; van der Harst P.; Desch K.C.; Kooner J.S.; Ohlsson C.; Hayward C.; Lehtimaki T.; Shuldiner A.R.; Arnett D.K.; Beilin L.J.; Robino A.; Froguel P.; Pirastu M.; Jess T.; Koenig W.; Loos R.J.F.; Evans D.A.; Schmidt H.; Smith G.D.; Slagboom P.E.; Eiriksdottir G.; Morris A.P.; Psaty B.M.; Tracy R.P.; Nolte I.M.; Boerwinkle E.; Visvikis-Siest S.; Reiner A.P.; Gross M.; Bis J.C.; Franke L.; Franco O.H.; Benjamin E.J.; Chasman D.I.; Dupuis J.; Snieder H.; Dehghan A.; Alizadeh B.Z./titolo:Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders/doi:10.1016%2Fj.ajhg.2018.09.009/rivista:American journal of human genetics/anno:2018/pagina_da:691/pagina_a:706/intervallo_pagine:691–706/volume:103, Ligthart, S, Vaez, A, Võsa, U, Stathopoulou, M G, de Vries, P S, Prins, B P, Van der Most, P J, Tanaka, T, Naderi, E, Rose, L M, Wu, Y, Karlsson, R, Barbalic, M, Lin, H, Pool, R, Zhu, G, Macé, A, Sidore, C, Trompet, S, Mangino, M, Sabater-Lleal, M, Kemp, J P, Abbasi, A, Kacprowski, T, Verweij, N, Smith, A V, Huang, T, Marzi, C, Feitosa, M F, Lohman, K K, Kleber, M E, Milaneschi, Y, Mueller, C, Huq, M, Vlachopoulou, E, Lyytikäinen, L P, Oldmeadow, C, Deelen, J, Perola, M, Zhao, J, Davey-Smith, G, Hicks, A, Timpson, N, St. Pourcain, B, Soranzo, N, Paternoster, L, Evans, D M & Hicks, A & Palmer, L J & Davey-Smith, G 2018, ' Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders ', American Journal of Human Genetics, vol. 103, no. 5, pp. 691-706 . https://doi.org/10.1016/j.ajhg.2018.09.009, American Journal of Human Genetics, 103(5), 691-706, AMERICAN JOURNAL OF HUMAN GENETICS, American Journal of Human Genetics, Elsevier (Cell Press), 2018, 103 (5), pp.691-706. ⟨10.1016/j.ajhg.2018.09.009⟩, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, Lifelines Cohort Study 2018, ' Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders ', American journal of human genetics, vol. 103, no. 5, pp. 691-706 . https://doi.org/10.1016/j.ajhg.2018.09.009
- Accession number :
- edsair.doi.dedup.....eefb48775cf207877807bd9799537354
- Full Text :
- https://doi.org/10.1016/j.ajhg.2018.09.009