| Autor: |
Albert Hofman, Megan L. Grove, Jennifer A. Brody, Adolfo Correa, Kim Lawson, Jose M. Ordovas, Yingchang Lu, André G. Uitterlinden, Riccardo E. Marioni, Nathan O. Stitziel, Oscar H. Franco, Yongmei Liu, Ingrid B. Borecki, Aron Y. Joon, Lindsay M. Reynolds, Ozren Polasek, Kelli K. Ryckman, Muredach P. Reilly, Johanna Jakobsdottir, Abbas Dehghan, L. Adrienne Cupples, Tamara B. Harris, Michael Griswold, Judy Wang, Christopher S. Carlson, Caroline Hayward, Leslie A. Lange, Stephen S. Rich, Kenneth Rice, Jacy R Crosby, Diego Ardissino, Charles Kooperberg, Gudny Eiriksdottir, Rachel H. Mackey, Ani Manichaikul, Martin Farrall, Jennifer E. Huffman, Albert V. Smith, Vilmundur Gudnason, Aniruddh P. Patel, Ruth J. F. Loos, Sumeet A. Khetarpal, Daniel J. Rader, Domenico Girelli, Eric Boerwinkle, Qunyuan Zhang, Valeska Redon, Anuj Goel, Cornelia M. van Duijn, Bruce M. Psaty, Ruth McPherson, Piera Angelica Merlini, Daniel Levy, Ian J. Deary, Christopher J. O'Donnell, Kurt Lohman, Josyf C. Mychaleckyj, Brian W. Davis, Mary F. Feitosa, Kent D. Taylor, James S. Pankow, Marju Orho-Melander, Alanna C. Morrison, Igor Rudan, Alexander P. Reiner, William E. Kraus, Ulrike Peters, Paul L. Auer, Paolo Zanoni, Svati H. Shah, Olle Melander, Jennifer G. Robinson, Joshua C. Bis, Erwin P. Bottinger, Mingyao Li, George Hindy, Omri Gottesman, Stefano Duga, Herman A. Taylor, Y.-D. Ida Chen, David S. Siscovick, Aaron Isaacs, Michael Y. Tsai, Sekar Kathiresan, James G. Wilson, Pamela J. Schreiner, Nicola Martinelli, Myriam Fornage, Serkalem Demissie, Lenore J. Launer, Hugh Watkins, Arend Voorman, Jerome I. Rotter, Jeanette M. Stafford, John M. Starr, Gina M. Peloso, Rosanna Asselta, Gail Davies, Rebecca D. Jackson |
| Přispěvatelé: |
Epidemiology, Internal Medicine |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
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| Zdroj: |
American Journal of Human Genetics, 94(2), 223-232. Cell Press
American Journal of Human Genetics, 94(2), 223-32. Cell Press |
| ISSN: |
0002-9297 |
| Popis: |
Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121*], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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