دورية أكاديمية
Mendelian randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits
| العنوان: | Mendelian randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits |
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| المؤلفون: | Porcu, Eleonora, Rüeger, Sina, Lepik, Kaido, Agbessi, Mawusse, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Bonder, Marc Jan, Boomsma, Dorret, Christiansen, Mark, Claringbould, Annique, Deelen, Patrick, Esko, Tonu, Fave, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Gregory, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kahonen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg-Guzman, Jaanika, Kukushkina, Viktorija, Lee, Bernett, Lehtimaki, Terho, Löffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Nivard, Michel, Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ripatti, Samuli, Rotzschke, Olaf, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppala, Ilkka, Slagboom, Eline P., Stehouwer, Coen D. A., Stumvoll, Michael, Sullivan, Patrick, Hoen, Peter A. C. 't, Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tonjes, Anke, Dongen, Jenny van, Iterson, Maarten van, Meurs, Joyce van, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Volker, Uwe, Vosa, Urmo, Westra, Harm-Jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Beekman, Marian, Boomsma, Dorret I., Bot, Jan, Deelen, Joris, Hofman, Bert A., Hottenga, Jouke J., Isaacs, Aaron, Jhamai, P. Mila, Kielbasa, Szymon M., Lakenberg, Nico, Luijk, Rene, Mei, Hailiang, Moed, Matthijs, Nooren, Irene, Pool, Rene, Schalkwijk, Casper G., Slagboom, P. Eline, Suchiman, H. Eka D., Swertz, Morris A., Tigchelaar, Ettje F., Uitterlinden, Andre G., Berg, Leonard H. van den, Breggen, Ruud van der, Kallen, Carla J. H. van der, Dijk, Freerk van, Duijn, Cornelia M. van, Galen, Michiel van, Greevenbroek, Marleen M. J. van, Heemst, Diana van, Rooij, Jeroen van, Hof, Peter van't, Zwet, Erik. W. van, Vermaat, Martijn, Verbiest, Michael, Verkerk, Marijn, Zhernakova, Dasha V., Zhernakova, Sasha, Santoni, Federico A., Reymond, Alexandre, Kutalik, Zoltan |
| المصدر: | Nature Communications |
| بيانات النشر: | Ludwig-Maximilians-Universität München |
| سنة النشر: | 2019 |
| المجموعة: | Open Access LMU (Ludwig-Maximilians-University Munich) |
| مصطلحات موضوعية: | Medizin, ddc:610 |
| الوصف: | Genome-wide association studies (GWAS) have identified thousands of variants associated with complex traits, but their biological interpretation often remains unclear. Most of these variants overlap with expression QTLs, indicating their potential involvement in regulation of gene expression. Here, we propose a transcriptome-wide summary statistics-based Mendelian Randomization approach (TWMR) that uses multiple SNPs as instruments and multiple gene expression traits as exposures, simultaneously. Applied to 43 human phenotypes, it uncovers 3,913 putatively causal gene-trait associations, 36% of which have no genome-wide significant SNP nearby in previous GWAS. Using independent association summary statistics, we find that the majority of these loci were missed by GWAS due to power issues. Noteworthy among these links is educational attainment-associated BSCL2, known to carry mutations leading to a Mendelian form of encephalopathy. We also find pleiotropic causal effects suggestive of mechanistic connections. TWMR better accounts for pleiotropy and has the potential to identify biological mechanisms underlying complex traits. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | Porcu, Eleonora; Rüeger, Sina; Lepik, Kaido; Agbessi, Mawusse; Ahsan, Habibul; Alves, Isabel; Andiappan, Anand; Arindrarto, Wibowo; Awadalla, Philip; Battle, Alexis; Beutner, Frank; Bonder, Marc Jan; Boomsma, Dorret; Christiansen, Mark; Claringbould, Annique; Deelen, Patrick; Esko, Tonu; Fave, Marie-Julie; Franke, Lude; Frayling, Timothy; Gharib, Sina A.; Gibson, Gregory; Heijmans, Bastiaan T.; Hemani, Gibran; Jansen, Rick; Kahonen, Mika; Kalnapenkis, Anette; Kasela, Silva; Kettunen, Johannes; Kim, Yungil; Kirsten, Holger; Kovacs, Peter; Krohn, Knut; Kronberg-Guzman, Jaanika; Kukushkina, Viktorija; Lee, Bernett; Lehtimaki, Terho; Löffler, Markus; Marigorta, Urko M.; Mei, Hailang; Milani, Lili; Montgomery, Grant W.; Müller-Nurasyid, Martina; Nauck, Matthias; Nivard, Michel; Penninx, Brenda; Perola, Markus; Pervjakova, Natalia; Pierce, Brandon L.; Powell, Joseph; Prokisch, Holger; Psaty, Bruce M.; Raitakari, Olli T.; Ripatti, Samuli; Rotzschke, Olaf; Saha, Ashis; Scholz, Markus; Schramm, Katharina; Seppala, Ilkka; Slagboom, Eline P.; Stehouwer, Coen D. A.; Stumvoll, Michael; Sullivan, Patrick; Hoen, Peter A. C. 't; Teumer, Alexander; Thiery, Joachim; Tong, Lin; Tonjes, Anke; Dongen, Jenny van; Iterson, Maarten van; Meurs, Joyce van; Veldink, Jan H.; Verlouw, Joost; Visscher, Peter M.; Volker, Uwe; Vosa, Urmo; Westra, Harm-Jan; Wijmenga, Cisca; Yaghootkar, Hanieh; Yang, Jian; Zeng, Biao; Zhang, Futao; Arindrarto, Wibowo; Beekman, Marian; Boomsma, Dorret I.; Bot, Jan; Deelen, Joris; Deelen, Patrick; Franke, Lude; Heijmans, Bastiaan T.; Hofman, Bert A.; Hottenga, Jouke J.; Isaacs, Aaron; Bonder, Marc Jan; Jhamai, P. Mila; Jansen, Rick; Kielbasa, Szymon M.; Lakenberg, Nico; Luijk, Rene; Mei, Hailiang; Moed, Matthijs; Nooren, Irene; Pool, Rene; Schalkwijk, Casper G.; Slagboom, P. Eline; Stehouwer, Coen D. A.; Suchiman, H. Eka D.; Swertz, Morris A.; Tigchelaar, Ettje F.; Uitterlinden, Andre G.; Berg, Leonard H. van den; Breggen, Ruud van der; Kallen, Carla J. H. van der; Dijk, Freerk van; Dongen, Jenny van; Duijn, Cornelia M. van; Galen, Michiel van; Greevenbroek, Marleen M. J. van orcid:0000-0002-2989-1631; Heemst, Diana van; Iterson, Maarten van; Meurs, Joyce van; Rooij, Jeroen van; Hof, Peter van't; Zwet, Erik. W. van; Vermaat, Martijn; Veldink, Jan H.; Verbiest, Michael; Verkerk, Marijn; Wijmenga, Cisca; Zhernakova, Dasha V.; Zhernakova, Sasha; Santoni, Federico A.; Reymond, Alexandre; Kutalik, Zoltan (2019): Mendelian randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits. In: Nature Communications, Vol. 10, 3300 [PDF, 1MB]; https://epub.ub.uni-muenchen.de/79560/1/s41467-019-10936-0.pdfTest; http://nbn-resolving.de/urn:nbn:de:bvb:19-epub-79560-8Test; https://epub.ub.uni-muenchen.de/79560Test/ |
| DOI: | 10.1038/s41467-019-10936-0 |
| الإتاحة: | https://doi.org/10.1038/s41467-019-10936-0Test https://epub.ub.uni-muenchen.de/79560/1/s41467-019-10936-0.pdfTest https://epub.ub.uni-muenchen.de/79560Test/ http://nbn-resolving.de/urn:nbn:de:bvb:19-epub-79560-8Test |
| رقم الانضمام: | edsbas.B5218DE7 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-019-10936-0 |
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