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Pregled bibliografske jedinice broj: 1238608

Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders

Ligthart, Symen; Vaez, Ahmad; Võsa, Urmo; Stathopoulou, Maria G.; de Vries, Paul S.; Prins, Bram P.; Van der Most, Peter J.; Tanaka, Toshiko; Naderi, Elnaz; Rose, Lynda M. et al.
Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders // The American Journal of Human Genetics, 103 (2018), 5; 691-706 doi:10.1016/j.ajhg.2018.09.009 (međunarodna recenzija, članak, znanstveni)

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Naslov
Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders

Autori
Ligthart, Symen ; Vaez, Ahmad ; Võsa, Urmo ; Stathopoulou, Maria G. ; de Vries, Paul S. ; Prins, Bram P. ; Van der Most, Peter J. ; Tanaka, Toshiko ; Naderi, Elnaz ; Rose, Lynda M. ; Wu, Ying ; Karlsson, Robert ; Barbalic, Maja ; Lin, Honghuang ; Pool, René ; Zhu, Gu ; Macé, Aurélien ; Sidore, Carlo ; Trompet, Stella ; Mangino, Massimo ; Sabater-Lleal, Maria ; Kemp, John P. ; Abbasi, Ali ; Kacprowski, Tim ; Verweij, Niek ; Smith, Albert V. ; Huang, Tao ; Marzi, Carola ; Feitosa, Mary F. ; Lohman, Kurt K. ; Kleber, Marcus E. ; Milaneschi, Yuri ; Mueller, Christian ; Huq, Mahmudul ; Vlachopoulou, Efthymia ; Lyytikäinen, Leo-Pekka ; Oldmeadow, Christopher ; Deelen, Joris ; Perola, Markus ; Zhao, Jing Hua ; Feenstra, Bjarke ; Amini, Marzyeh ; Lahti, Jari ; Schraut, Katharina E. ; Fornage, Myriam ; Suktitipat, Bhoom ; Chen, Wei-Min ; Li, Xiaohui ; Nutile, Teresa ; Malerba, Giovanni ; Luan, Jian’an ; Bak, Tom ; Schork, Nicholas ; Del Greco M., Fabiola ; Thiering, Elisabeth ; Mahajan, Anubha ; Marioni, Riccardo E. ; Mihailov, Evelin ; Eriksson, Joel ; Ozel, Ayse Bilge ; Zhang, Weihua ; Nethander, Maria ; Cheng, Yu-Ching ; Aslibekyan, Stella ; Ang, Wei ; Gandin, Ilaria ; Yengo, Loïc ; Portas, Laura ; Kooperberg, Charles ; Hofer, Edith ; Rajan, Kumar B. ; Schurmann, Claudia ; den Hollander, Wouter ; Ahluwalia, Tarunveer S. ; Zhao, Jing ; Draisma, Harmen H.M. ; Ford, Ian ; Timpson, Nicholas ; Teumer, Alexander ; Huang, Hongyan ; Wahl, Simone ; Liu, YongMei ; Huang, Jie ; Uh, Hae-Won ; Geller, Frank ; Joshi, Peter K. ; Yanek, Lisa R. ; Trabetti, Elisabetta ; Lehne, Benjamin ; Vozzi, Diego ; Verbanck, Marie ; Biino, Ginevra ; Saba, Yasaman ; Meulenbelt, Ingrid ; O’Connell, Jeff R. ; Laakso, Markku ; Giulianini, Franco ; Magnusson, Patrik K.E. ; Ballantyne, Christie M. ; Hottenga, Jouke Jan ; Montgomery, Grant W. ; Rivadineira, Fernando ; Rueedi, Rico ; Steri, Maristella ; Herzig, Karl-Heinz ; Stott, David J. ; Menni, Cristina ; Frånberg, Mattias ; St. Pourcain, Beate ; Felix, Stephan B. ; Pers, Tune H. ; Bakker, Stephan J.L. ; Kraft, Peter ; Peters, Annette ; Vaidya, Dhananjay ; Delgado, Graciela ; Smit, Johannes H. ; Großmann, Vera ; Sinisalo, Juha ; Seppälä, Ilkka ; Williams, Stephen R. ; Holliday, Elizabeth G. ; Moed, Matthijs ; Langenberg, Claudia ; Räikkönen, Katri ; Ding, Jingzhong ; Campbell, Harry ; Sale, Michele M. ; Chen, Yii-Der I. ; James, Alan L. ; Ruggiero, Daniela ; Soranzo, Nicole ; Hartman, Catharina A. ; Smith, Erin N. ; Berenson, Gerald S. ; Fuchsberger, Christian ; Hernandez, Dena ; Tiesler, Carla M.T. ; Giedraitis, Vilmantas ; Liewald, David ; Fischer, Krista ; Mellström, Dan ; Larsson, Anders ; Wang, Yunmei ; Scott, William R. ; Lorentzon, Matthias ; Beilby, John ; Ryan, Kathleen A. ; Pennell, Craig E. ; Vuckovic, Dragana ; Balkau, Beverly ; Concas, Maria Pina ; Schmidt, Reinhold ; Mendes de Leon, Carlos F. ; Bottinger, Erwin P. ; Kloppenburg, Margreet ; Paternoster, Lavinia ; Boehnke, Michael ; Musk, A.W. ; Willemsen, Gonneke ; Evans, David M. ; Madden, Pamela A.F. ; Kähönen, Mika ; Kutalik, Zoltán ; Zoledziewska, Magdalena ; Karhunen, Ville ; Kritchevsky, Stephen B. ; Sattar, Naveed ; Lachance, Genevieve ; Clarke, Robert ; Harris, Tamara B. ; Raitakari, Olli T. ; Attia, John R. ; van Heemst, Diana ; Kajantie, Eero ; Sorice, Rossella ; Gambaro, Giovanni ; Scott, Robert A. ; Hicks, Andrew A. ; Ferrucci, Luigi ; Standl, Marie ; Lindgren, Cecilia M. ; Starr, John M. ; Karlsson, Magnus ; Lind, Lars ; Li, Jun Z. ; Chambers, John C. ; Mori, Trevor A. ; de Geus, Eco J.C.N. ; Heath, Andrew C. ; Martin, Nicholas G. ; Auvinen, Juha ; Buckley, Brendan M. ; de Craen, Anton J.M. ; Waldenberger, Melanie ; Strauch, Konstantin ; Meitinger, Thomas ; Scott, Rodney J. ; McEvoy, Mark ; Beekman, Marian ; Bombieri, Cristina ; Ridker, Paul M. ; Mohlke, Karen L. ; Pedersen, Nancy L. ; Morrison, Alanna C. ; Boomsma, Dorret I. ; Whitfield, John B. ; Strachan, David P. ; Hofman, Albert ; Vollenweider, Peter ; Cucca, Francesco ; Jarvelin, Marjo-Riitta ; Jukema, J. Wouter ; Spector, Tim D. ; Hamsten, Anders ; Zeller, Tanja ; Uitterlinden, André G. ; Nauck, Matthias ; Gudnason, Vilmundur ; Qi, Lu ; Grallert, Harald ; Borecki, Ingrid B. ; Rotter, Jerome I. ; März, Winfried ; Wild, Philipp S. ; Lokki, Marja-Liisa ; Boyle, Michael ; Salomaa, Veikko ; Melbye, Mads ; et al.

Izvornik
The American Journal of Human Genetics (0002-9297) 103 (2018), 5; 691-706

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
C-reactive protein ; DEPICT ; Mendelian randomization ; coronary artery disease ; genome-wide association study ; inflammation ; inflammatory disorders ; schizophrenia ; system biology

Sažetak
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.

Izvorni jezik
Engleski



POVEZANOST RADA

Ustanove:
Medicinski fakultet, Split

Profili:

Avatar Url Maja Barbalić (autor)

Poveznice na cjeloviti tekst rada:

doi

Citiraj ovu publikaciju:

Ligthart, Symen; Vaez, Ahmad; Võsa, Urmo; Stathopoulou, Maria G.; de Vries, Paul S.; Prins, Bram P.; Van der Most, Peter J.; Tanaka, Toshiko; Naderi, Elnaz; Rose, Lynda M. et al.
Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders // The American Journal of Human Genetics, 103 (2018), 5; 691-706 doi:10.1016/j.ajhg.2018.09.009 (međunarodna recenzija, članak, znanstveni)
Ligthart, S., Vaez, A., Võsa, U., Stathopoulou, M., de Vries, P., Prins, B., Van der Most, P., Tanaka, T., Naderi, E. & Rose, L. (2018) Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders. The American Journal of Human Genetics, 103 (5), 691-706 doi:10.1016/j.ajhg.2018.09.009.
@article{article, author = {Ligthart, Symen and Vaez, Ahmad and V\~{o}sa, Urmo and Stathopoulou, Maria G. and de Vries, Paul S. and Prins, Bram P. and Van der Most, Peter J. and Tanaka, Toshiko and Naderi, Elnaz and Rose, Lynda M. and Wu, Ying and Karlsson, Robert and Barbalic, Maja and Lin, Honghuang and Pool, Ren\'{e} and Zhu, Gu and Mac\'{e}, Aur\'{e}lien and Sidore, Carlo and Trompet, Stella and Mangino, Massimo and Sabater-Lleal, Maria and Kemp, John P. and Abbasi, Ali and Kacprowski, Tim and Verweij, Niek and Smith, Albert V. and Huang, Tao and Marzi, Carola and Feitosa, Mary F. and Lohman, Kurt K. and Kleber, Marcus E. and Milaneschi, Yuri and Mueller, Christian and Huq, Mahmudul and Vlachopoulou, Efthymia and Lyytik\"{a}inen, Leo-Pekka and Oldmeadow, Christopher and Deelen, Joris and Perola, Markus and Zhao, Jing Hua and Feenstra, Bjarke and Amini, Marzyeh and Lahti, Jari and Schraut, Katharina E. and Fornage, Myriam and Suktitipat, Bhoom and Chen, Wei-Min and Li, Xiaohui and Nutile, Teresa and Malerba, Giovanni and Luan, Jian’an and Bak, Tom and Schork, Nicholas and Del Greco M., Fabiola and Thiering, Elisabeth and Mahajan, Anubha and Marioni, Riccardo E. and Mihailov, Evelin and Eriksson, Joel and Ozel, Ayse Bilge and Zhang, Weihua and Nethander, Maria and Cheng, Yu-Ching and Aslibekyan, Stella and Ang, Wei and Gandin, Ilaria and Yengo, Lo\"{\i}c and Portas, Laura and Kooperberg, Charles and Hofer, Edith and Rajan, Kumar B. and Schurmann, Claudia and den Hollander, Wouter and Ahluwalia, Tarunveer S. and Zhao, Jing and Draisma, Harmen H.M. and Ford, Ian and Timpson, Nicholas and Teumer, Alexander and Huang, Hongyan and Wahl, Simone and Liu, YongMei and Huang, Jie and Uh, Hae-Won and Geller, Frank and Joshi, Peter K. and Yanek, Lisa R. and Trabetti, Elisabetta and Lehne, Benjamin and Vozzi, Diego and Verbanck, Marie and Biino, Ginevra and Saba, Yasaman and Meulenbelt, Ingrid and O’Connell, Jeff R. and Laakso, Markku and Giulianini, Franco and Magnusson, Patrik K.E. and Ballantyne, Christie M. and Hottenga, Jouke Jan and Montgomery, Grant W. and Rivadineira, Fernando and Rueedi, Rico and Steri, Maristella and Herzig, Karl-Heinz and Stott, David J. and Menni, Cristina and Fr\aanberg, Mattias and St. Pourcain, Beate and Felix, Stephan B. and Pers, Tune H. and Bakker, Stephan J.L. and Kraft, Peter and Peters, Annette and Vaidya, Dhananjay and Delgado, Graciela and Smit, Johannes H. and Großmann, Vera and Sinisalo, Juha and Sepp\"{a}l\"{a}, Ilkka and Williams, Stephen R. and Holliday, Elizabeth G. and Moed, Matthijs and Langenberg, Claudia and R\"{a}ikk\"{o}nen, Katri and Ding, Jingzhong and Campbell, Harry and Sale, Michele M. and Chen, Yii-Der I. and James, Alan L. and Ruggiero, Daniela and Soranzo, Nicole and Hartman, Catharina A. and Smith, Erin N. and Berenson, Gerald S. and Fuchsberger, Christian and Hernandez, Dena and Tiesler, Carla M.T. and Giedraitis, Vilmantas and Liewald, David and Fischer, Krista and Mellstr\"{o}m, Dan and Larsson, Anders and Wang, Yunmei and Scott, William R. and Lorentzon, Matthias and Beilby, John and Ryan, Kathleen A. and Pennell, Craig E. and Vuckovic, Dragana and Balkau, Beverly and Concas, Maria Pina and Schmidt, Reinhold and Mendes de Leon, Carlos F. and Bottinger, Erwin P. and Kloppenburg, Margreet and Paternoster, Lavinia and Boehnke, Michael and Musk, A.W. and Willemsen, Gonneke and Evans, David M. and Madden, Pamela A.F. and K\"{a}h\"{o}nen, Mika and Kutalik, Zolt\'{a}n and Zoledziewska, Magdalena and Karhunen, Ville and Kritchevsky, Stephen B. and Sattar, Naveed and Lachance, Genevieve and Clarke, Robert and Harris, Tamara B. and Raitakari, Olli T. and Attia, John R. and van Heemst, Diana and Kajantie, Eero and Sorice, Rossella and Gambaro, Giovanni and Scott, Robert A. and Hicks, Andrew A. and Ferrucci, Luigi and Standl, Marie and Lindgren, Cecilia M. and Starr, John M. and Karlsson, Magnus and Lind, Lars and Li, Jun Z. and Chambers, John C. and Mori, Trevor A. and de Geus, Eco J.C.N. and Heath, Andrew C. and Martin, Nicholas G. and Auvinen, Juha and Buckley, Brendan M. and de Craen, Anton J.M. and Waldenberger, Melanie and Strauch, Konstantin and Meitinger, Thomas and Scott, Rodney J. and McEvoy, Mark and Beekman, Marian and Bombieri, Cristina and Ridker, Paul M. and Mohlke, Karen L. and Pedersen, Nancy L. and Morrison, Alanna C. and Boomsma, Dorret I. and Whitfield, John B. and Strachan, David P. and Hofman, Albert and Vollenweider, Peter and Cucca, Francesco and Jarvelin, Marjo-Riitta and Jukema, J. Wouter and Spector, Tim D. and Hamsten, Anders and Zeller, Tanja and Uitterlinden, Andr\'{e} G. and Nauck, Matthias and Gudnason, Vilmundur and Qi, Lu and Grallert, Harald and Borecki, Ingrid B. and Rotter, Jerome I. and M\"{a}rz, Winfried and Wild, Philipp S. and Lokki, Marja-Liisa and Boyle, Michael and Salomaa, Veikko and Melbye, Mads}, year = {2018}, pages = {691-706}, DOI = {10.1016/j.ajhg.2018.09.009}, keywords = {C-reactive protein, DEPICT, Mendelian randomization, coronary artery disease, genome-wide association study, inflammation, inflammatory disorders, schizophrenia, system biology}, journal = {The American Journal of Human Genetics}, doi = {10.1016/j.ajhg.2018.09.009}, volume = {103}, number = {5}, issn = {0002-9297}, title = {Genome Analyses of and gt;200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders}, keyword = {C-reactive protein, DEPICT, Mendelian randomization, coronary artery disease, genome-wide association study, inflammation, inflammatory disorders, schizophrenia, system biology} }
@article{article, author = {Ligthart, Symen and Vaez, Ahmad and V\~{o}sa, Urmo and Stathopoulou, Maria G. and de Vries, Paul S. and Prins, Bram P. and Van der Most, Peter J. and Tanaka, Toshiko and Naderi, Elnaz and Rose, Lynda M. and Wu, Ying and Karlsson, Robert and Barbalic, Maja and Lin, Honghuang and Pool, Ren\'{e} and Zhu, Gu and Mac\'{e}, Aur\'{e}lien and Sidore, Carlo and Trompet, Stella and Mangino, Massimo and Sabater-Lleal, Maria and Kemp, John P. and Abbasi, Ali and Kacprowski, Tim and Verweij, Niek and Smith, Albert V. and Huang, Tao and Marzi, Carola and Feitosa, Mary F. and Lohman, Kurt K. and Kleber, Marcus E. and Milaneschi, Yuri and Mueller, Christian and Huq, Mahmudul and Vlachopoulou, Efthymia and Lyytik\"{a}inen, Leo-Pekka and Oldmeadow, Christopher and Deelen, Joris and Perola, Markus and Zhao, Jing Hua and Feenstra, Bjarke and Amini, Marzyeh and Lahti, Jari and Schraut, Katharina E. and Fornage, Myriam and Suktitipat, Bhoom and Chen, Wei-Min and Li, Xiaohui and Nutile, Teresa and Malerba, Giovanni and Luan, Jian’an and Bak, Tom and Schork, Nicholas and Del Greco M., Fabiola and Thiering, Elisabeth and Mahajan, Anubha and Marioni, Riccardo E. and Mihailov, Evelin and Eriksson, Joel and Ozel, Ayse Bilge and Zhang, Weihua and Nethander, Maria and Cheng, Yu-Ching and Aslibekyan, Stella and Ang, Wei and Gandin, Ilaria and Yengo, Lo\"{\i}c and Portas, Laura and Kooperberg, Charles and Hofer, Edith and Rajan, Kumar B. and Schurmann, Claudia and den Hollander, Wouter and Ahluwalia, Tarunveer S. and Zhao, Jing and Draisma, Harmen H.M. and Ford, Ian and Timpson, Nicholas and Teumer, Alexander and Huang, Hongyan and Wahl, Simone and Liu, YongMei and Huang, Jie and Uh, Hae-Won and Geller, Frank and Joshi, Peter K. and Yanek, Lisa R. and Trabetti, Elisabetta and Lehne, Benjamin and Vozzi, Diego and Verbanck, Marie and Biino, Ginevra and Saba, Yasaman and Meulenbelt, Ingrid and O’Connell, Jeff R. and Laakso, Markku and Giulianini, Franco and Magnusson, Patrik K.E. and Ballantyne, Christie M. and Hottenga, Jouke Jan and Montgomery, Grant W. and Rivadineira, Fernando and Rueedi, Rico and Steri, Maristella and Herzig, Karl-Heinz and Stott, David J. and Menni, Cristina and Fr\aanberg, Mattias and St. Pourcain, Beate and Felix, Stephan B. and Pers, Tune H. and Bakker, Stephan J.L. and Kraft, Peter and Peters, Annette and Vaidya, Dhananjay and Delgado, Graciela and Smit, Johannes H. and Großmann, Vera and Sinisalo, Juha and Sepp\"{a}l\"{a}, Ilkka and Williams, Stephen R. and Holliday, Elizabeth G. and Moed, Matthijs and Langenberg, Claudia and R\"{a}ikk\"{o}nen, Katri and Ding, Jingzhong and Campbell, Harry and Sale, Michele M. and Chen, Yii-Der I. and James, Alan L. and Ruggiero, Daniela and Soranzo, Nicole and Hartman, Catharina A. and Smith, Erin N. and Berenson, Gerald S. and Fuchsberger, Christian and Hernandez, Dena and Tiesler, Carla M.T. and Giedraitis, Vilmantas and Liewald, David and Fischer, Krista and Mellstr\"{o}m, Dan and Larsson, Anders and Wang, Yunmei and Scott, William R. and Lorentzon, Matthias and Beilby, John and Ryan, Kathleen A. and Pennell, Craig E. and Vuckovic, Dragana and Balkau, Beverly and Concas, Maria Pina and Schmidt, Reinhold and Mendes de Leon, Carlos F. and Bottinger, Erwin P. and Kloppenburg, Margreet and Paternoster, Lavinia and Boehnke, Michael and Musk, A.W. and Willemsen, Gonneke and Evans, David M. and Madden, Pamela A.F. and K\"{a}h\"{o}nen, Mika and Kutalik, Zolt\'{a}n and Zoledziewska, Magdalena and Karhunen, Ville and Kritchevsky, Stephen B. and Sattar, Naveed and Lachance, Genevieve and Clarke, Robert and Harris, Tamara B. and Raitakari, Olli T. and Attia, John R. and van Heemst, Diana and Kajantie, Eero and Sorice, Rossella and Gambaro, Giovanni and Scott, Robert A. and Hicks, Andrew A. and Ferrucci, Luigi and Standl, Marie and Lindgren, Cecilia M. and Starr, John M. and Karlsson, Magnus and Lind, Lars and Li, Jun Z. and Chambers, John C. and Mori, Trevor A. and de Geus, Eco J.C.N. and Heath, Andrew C. and Martin, Nicholas G. and Auvinen, Juha and Buckley, Brendan M. and de Craen, Anton J.M. and Waldenberger, Melanie and Strauch, Konstantin and Meitinger, Thomas and Scott, Rodney J. and McEvoy, Mark and Beekman, Marian and Bombieri, Cristina and Ridker, Paul M. and Mohlke, Karen L. and Pedersen, Nancy L. and Morrison, Alanna C. and Boomsma, Dorret I. and Whitfield, John B. and Strachan, David P. and Hofman, Albert and Vollenweider, Peter and Cucca, Francesco and Jarvelin, Marjo-Riitta and Jukema, J. Wouter and Spector, Tim D. and Hamsten, Anders and Zeller, Tanja and Uitterlinden, Andr\'{e} G. and Nauck, Matthias and Gudnason, Vilmundur and Qi, Lu and Grallert, Harald and Borecki, Ingrid B. and Rotter, Jerome I. and M\"{a}rz, Winfried and Wild, Philipp S. and Lokki, Marja-Liisa and Boyle, Michael and Salomaa, Veikko and Melbye, Mads}, year = {2018}, pages = {691-706}, DOI = {10.1016/j.ajhg.2018.09.009}, keywords = {C-reactive protein, DEPICT, Mendelian randomization, coronary artery disease, genome-wide association study, inflammation, inflammatory disorders, schizophrenia, system biology}, journal = {The American Journal of Human Genetics}, doi = {10.1016/j.ajhg.2018.09.009}, volume = {103}, number = {5}, issn = {0002-9297}, title = {Genome Analyses of and gt;200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders}, keyword = {C-reactive protein, DEPICT, Mendelian randomization, coronary artery disease, genome-wide association study, inflammation, inflammatory disorders, schizophrenia, system biology} }

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