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Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels
BACKGROUND: So far, more than 170 loci have been associated with circulating lipid levels through genome-wide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this st...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
BMJ Publishing Group
2016
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941146/ https://www.ncbi.nlm.nih.gov/pubmed/27036123 http://dx.doi.org/10.1136/jmedgenet-2015-103439 |
| _version_ | 1782442253157924864 |
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| author | van Leeuwen, Elisabeth M Sabo, Aniko Bis, Joshua C Huffman, Jennifer E Manichaikul, Ani Smith, Albert V Feitosa, Mary F Demissie, Serkalem Joshi, Peter K Duan, Qing Marten, Jonathan van Klinken, Jan B Surakka, Ida Nolte, Ilja M Zhang, Weihua Mbarek, Hamdi Li-Gao, Ruifang Trompet, Stella Verweij, Niek Evangelou, Evangelos Lyytikäinen, Leo-Pekka Tayo, Bamidele O Deelen, Joris van der Most, Peter J van der Laan, Sander W Arking, Dan E Morrison, Alanna Dehghan, Abbas Franco, Oscar H Hofman, Albert Rivadeneira, Fernando Sijbrands, Eric J Uitterlinden, Andre G Mychaleckyj, Josyf C Campbell, Archie Hocking, Lynne J Padmanabhan, Sandosh Brody, Jennifer A Rice, Kenneth M White, Charles C Harris, Tamara Isaacs, Aaron Campbell, Harry Lange, Leslie A Rudan, Igor Kolcic, Ivana Navarro, Pau Zemunik, Tatijana Salomaa, Veikko Kooner, Angad S Kooner, Jaspal S Lehne, Benjamin Scott, William R Tan, Sian-Tsung de Geus, Eco J Milaneschi, Yuri Penninx, Brenda W J H Willemsen, Gonneke de Mutsert, Renée Ford, Ian Gansevoort, Ron T Segura-Lepe, Marcelo P Raitakari, Olli T Viikari, Jorma S Nikus, Kjell Forrester, Terrence McKenzie, Colin A de Craen, Anton J M de Ruijter, Hester M Pasterkamp, Gerard Snieder, Harold Oldehinkel, Albertine J Slagboom, P Eline Cooper, Richard S Kähönen, Mika Lehtimäki, Terho Elliott, Paul van der Harst, Pim Jukema, J Wouter Mook-Kanamori, Dennis O Boomsma, Dorret I Chambers, John C Swertz, Morris Ripatti, Samuli Willems van Dijk, Ko Vitart, Veronique Polasek, Ozren Hayward, Caroline Wilson, James G Wilson, James F Gudnason, Vilmundur Rich, Stephen S Psaty, Bruce M Borecki, Ingrid B Boerwinkle, Eric Rotter, Jerome I Cupples, L Adrienne van Duijn, Cornelia M |
| author_facet | van Leeuwen, Elisabeth M Sabo, Aniko Bis, Joshua C Huffman, Jennifer E Manichaikul, Ani Smith, Albert V Feitosa, Mary F Demissie, Serkalem Joshi, Peter K Duan, Qing Marten, Jonathan van Klinken, Jan B Surakka, Ida Nolte, Ilja M Zhang, Weihua Mbarek, Hamdi Li-Gao, Ruifang Trompet, Stella Verweij, Niek Evangelou, Evangelos Lyytikäinen, Leo-Pekka Tayo, Bamidele O Deelen, Joris van der Most, Peter J van der Laan, Sander W Arking, Dan E Morrison, Alanna Dehghan, Abbas Franco, Oscar H Hofman, Albert Rivadeneira, Fernando Sijbrands, Eric J Uitterlinden, Andre G Mychaleckyj, Josyf C Campbell, Archie Hocking, Lynne J Padmanabhan, Sandosh Brody, Jennifer A Rice, Kenneth M White, Charles C Harris, Tamara Isaacs, Aaron Campbell, Harry Lange, Leslie A Rudan, Igor Kolcic, Ivana Navarro, Pau Zemunik, Tatijana Salomaa, Veikko Kooner, Angad S Kooner, Jaspal S Lehne, Benjamin Scott, William R Tan, Sian-Tsung de Geus, Eco J Milaneschi, Yuri Penninx, Brenda W J H Willemsen, Gonneke de Mutsert, Renée Ford, Ian Gansevoort, Ron T Segura-Lepe, Marcelo P Raitakari, Olli T Viikari, Jorma S Nikus, Kjell Forrester, Terrence McKenzie, Colin A de Craen, Anton J M de Ruijter, Hester M Pasterkamp, Gerard Snieder, Harold Oldehinkel, Albertine J Slagboom, P Eline Cooper, Richard S Kähönen, Mika Lehtimäki, Terho Elliott, Paul van der Harst, Pim Jukema, J Wouter Mook-Kanamori, Dennis O Boomsma, Dorret I Chambers, John C Swertz, Morris Ripatti, Samuli Willems van Dijk, Ko Vitart, Veronique Polasek, Ozren Hayward, Caroline Wilson, James G Wilson, James F Gudnason, Vilmundur Rich, Stephen S Psaty, Bruce M Borecki, Ingrid B Boerwinkle, Eric Rotter, Jerome I Cupples, L Adrienne van Duijn, Cornelia M |
| author_sort | van Leeuwen, Elisabeth M |
| collection | PubMed |
| description | BACKGROUND: So far, more than 170 loci have been associated with circulating lipid levels through genome-wide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels. METHODS: We used the 1000 Genomes Project as a reference panel for the imputations of GWAS data from ∼60 000 individuals in the discovery stage and ∼90 000 samples in the replication stage. RESULTS: Our study resulted in the identification of five new associations with circulating lipid levels at four loci. All four loci are within genes that can be linked biologically to lipid metabolism. One of the variants, rs116843064, is a damaging missense variant within the ANGPTL4 gene. CONCLUSIONS: This study illustrates that GWAS with high-scale imputation may still help us unravel the biological mechanism behind circulating lipid levels. |
| format | Online Article Text |
| id | pubmed-4941146 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2016 |
| publisher | BMJ Publishing Group |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-49411462016-07-13 Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels van Leeuwen, Elisabeth M Sabo, Aniko Bis, Joshua C Huffman, Jennifer E Manichaikul, Ani Smith, Albert V Feitosa, Mary F Demissie, Serkalem Joshi, Peter K Duan, Qing Marten, Jonathan van Klinken, Jan B Surakka, Ida Nolte, Ilja M Zhang, Weihua Mbarek, Hamdi Li-Gao, Ruifang Trompet, Stella Verweij, Niek Evangelou, Evangelos Lyytikäinen, Leo-Pekka Tayo, Bamidele O Deelen, Joris van der Most, Peter J van der Laan, Sander W Arking, Dan E Morrison, Alanna Dehghan, Abbas Franco, Oscar H Hofman, Albert Rivadeneira, Fernando Sijbrands, Eric J Uitterlinden, Andre G Mychaleckyj, Josyf C Campbell, Archie Hocking, Lynne J Padmanabhan, Sandosh Brody, Jennifer A Rice, Kenneth M White, Charles C Harris, Tamara Isaacs, Aaron Campbell, Harry Lange, Leslie A Rudan, Igor Kolcic, Ivana Navarro, Pau Zemunik, Tatijana Salomaa, Veikko Kooner, Angad S Kooner, Jaspal S Lehne, Benjamin Scott, William R Tan, Sian-Tsung de Geus, Eco J Milaneschi, Yuri Penninx, Brenda W J H Willemsen, Gonneke de Mutsert, Renée Ford, Ian Gansevoort, Ron T Segura-Lepe, Marcelo P Raitakari, Olli T Viikari, Jorma S Nikus, Kjell Forrester, Terrence McKenzie, Colin A de Craen, Anton J M de Ruijter, Hester M Pasterkamp, Gerard Snieder, Harold Oldehinkel, Albertine J Slagboom, P Eline Cooper, Richard S Kähönen, Mika Lehtimäki, Terho Elliott, Paul van der Harst, Pim Jukema, J Wouter Mook-Kanamori, Dennis O Boomsma, Dorret I Chambers, John C Swertz, Morris Ripatti, Samuli Willems van Dijk, Ko Vitart, Veronique Polasek, Ozren Hayward, Caroline Wilson, James G Wilson, James F Gudnason, Vilmundur Rich, Stephen S Psaty, Bruce M Borecki, Ingrid B Boerwinkle, Eric Rotter, Jerome I Cupples, L Adrienne van Duijn, Cornelia M J Med Genet Genome-Wide Studies BACKGROUND: So far, more than 170 loci have been associated with circulating lipid levels through genome-wide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels. METHODS: We used the 1000 Genomes Project as a reference panel for the imputations of GWAS data from ∼60 000 individuals in the discovery stage and ∼90 000 samples in the replication stage. RESULTS: Our study resulted in the identification of five new associations with circulating lipid levels at four loci. All four loci are within genes that can be linked biologically to lipid metabolism. One of the variants, rs116843064, is a damaging missense variant within the ANGPTL4 gene. CONCLUSIONS: This study illustrates that GWAS with high-scale imputation may still help us unravel the biological mechanism behind circulating lipid levels. BMJ Publishing Group 2016-07 2016-04-01 /pmc/articles/PMC4941146/ /pubmed/27036123 http://dx.doi.org/10.1136/jmedgenet-2015-103439 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ |
| spellingShingle | Genome-Wide Studies van Leeuwen, Elisabeth M Sabo, Aniko Bis, Joshua C Huffman, Jennifer E Manichaikul, Ani Smith, Albert V Feitosa, Mary F Demissie, Serkalem Joshi, Peter K Duan, Qing Marten, Jonathan van Klinken, Jan B Surakka, Ida Nolte, Ilja M Zhang, Weihua Mbarek, Hamdi Li-Gao, Ruifang Trompet, Stella Verweij, Niek Evangelou, Evangelos Lyytikäinen, Leo-Pekka Tayo, Bamidele O Deelen, Joris van der Most, Peter J van der Laan, Sander W Arking, Dan E Morrison, Alanna Dehghan, Abbas Franco, Oscar H Hofman, Albert Rivadeneira, Fernando Sijbrands, Eric J Uitterlinden, Andre G Mychaleckyj, Josyf C Campbell, Archie Hocking, Lynne J Padmanabhan, Sandosh Brody, Jennifer A Rice, Kenneth M White, Charles C Harris, Tamara Isaacs, Aaron Campbell, Harry Lange, Leslie A Rudan, Igor Kolcic, Ivana Navarro, Pau Zemunik, Tatijana Salomaa, Veikko Kooner, Angad S Kooner, Jaspal S Lehne, Benjamin Scott, William R Tan, Sian-Tsung de Geus, Eco J Milaneschi, Yuri Penninx, Brenda W J H Willemsen, Gonneke de Mutsert, Renée Ford, Ian Gansevoort, Ron T Segura-Lepe, Marcelo P Raitakari, Olli T Viikari, Jorma S Nikus, Kjell Forrester, Terrence McKenzie, Colin A de Craen, Anton J M de Ruijter, Hester M Pasterkamp, Gerard Snieder, Harold Oldehinkel, Albertine J Slagboom, P Eline Cooper, Richard S Kähönen, Mika Lehtimäki, Terho Elliott, Paul van der Harst, Pim Jukema, J Wouter Mook-Kanamori, Dennis O Boomsma, Dorret I Chambers, John C Swertz, Morris Ripatti, Samuli Willems van Dijk, Ko Vitart, Veronique Polasek, Ozren Hayward, Caroline Wilson, James G Wilson, James F Gudnason, Vilmundur Rich, Stephen S Psaty, Bruce M Borecki, Ingrid B Boerwinkle, Eric Rotter, Jerome I Cupples, L Adrienne van Duijn, Cornelia M Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels |
| title | Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels |
| title_full | Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels |
| title_fullStr | Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels |
| title_full_unstemmed | Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels |
| title_short | Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels |
| title_sort | meta-analysis of 49 549 individuals imputed with the 1000 genomes project reveals an exonic damaging variant in angptl4 determining fasting tg levels |
| topic | Genome-Wide Studies |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941146/ https://www.ncbi.nlm.nih.gov/pubmed/27036123 http://dx.doi.org/10.1136/jmedgenet-2015-103439 |
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