An APOO Pseudogene on Chromosome 5q Is Associated With Low-Density Lipoprotein Cholesterol Levels. Issue 13 (25th September 2018)

• Record Type: Journal Article
• Authors: Montasser, May E.; O'Hare, Elizabeth A.; Wang, Xiaochun; Howard, Alicia D.; McFarland, Rebecca; Perry, James A.; Ryan, Kathleen A.; Rice, Kenneth; Jaquish, Cashell E.; Shuldiner, Alan R.; Miller, Michael; Mitchell, Braxton D.; Zaghloul, Norann A.; Chang, Yen-Pei C.; Abe, Namiko; Abecasis, Goncalo; Albert, Christine; Allred, Nicholette P.; Almasy, Laura; Alonso, Alvaro; Ament, Seth; Anderson, Peter; Anugu, Pramod; Applebaum-Bowden, Debora; Arking, Dan; Arnett, Donna K; Ashley-Koch, Allison; Aslibekyan, Stella; Assimes, Tim; Auer, Paul; Avramopoulos, Dimitrios; Barnard, John; Barnes, Kathleen; Graham Barr, R.; Barron-Casella, Emily; Beaty, Terri; Becker, Diane; Becker, Lewis; Beer, Rebecca; Begum, Ferdouse; Beitelshees, Amber; Benjamin, Emelia; Bezerra, Marcos; Bielak, Larry; Bis, Joshua; Blackwell, Thomas; Blangero, John; Boerwinkle, Eric; Borecki, Ingrid; Bowler, Russel; Brody, Jennifer; Broeckel, Ulrich; Broome, Jai; Bunting, Karen; Burchard, Esteban; Cardwell, Jonathan; Carlson, Sara; Carty, Cara; Casaburi, Richard; Casella, James; Chaffin, Mark; Chang, Christy; Chasman, Daniel; Chavan, Sameer; Chen, Bo-Juen; Chen, Wei-Min; Ida Chen, Yii-Der; Cho, Michael; Choi, Seung Hoan; Chuang, Lee-Ming; Chung, Mina; Cornell, Elaine; Correa, Adolfo; Crandall, Carolyn; Crapo, James; Cupples, L Adrienne; Curran, Joanne; Curtis, Jeffrey; Custer, Brian; Damcott, Coleen; Darbar, Dawood; Das, Sayantan; David, Sean; Davis, Colleen; Daya, Michelle; de Andrade, Mariza; DeBaun, Michael; Deka, Ranjan; DeMeo, Dawn; Devine, Scott; Do, Ron; Duan, Qing; Duggirala, Ravi; Durda, Peter; Dutcher, Susan; Eaton, Charles; Ekunwe, Lynette; Ellinor, Patrick; Emery, Leslie; Farber, Charles; Farnam, Leanna; Fingerlin, Tasha; Flickinger, Matthew; Fornage, Myriam; Franceschini, Nora; Fu, Mao; Fullerton, Malia; Fulton, Lucinda; Gabriel, Stacey; Gan, Weiniu; Gao, Yan; Gass, Margery; Gelb, Bruce; Geng, Xiaoqi (Priscilla); Germer, Soren; Gignoux, Chris; Gladwin, Mark; Glahn, David; Gogarten, Stephanie; Gong, Da-Wei; Goring, Harald; Charles Gu, C.; Guan, Yue; Guo, Xiuqing; Haessler, Jeff; Hall, Michael; Harris, Daniel; Hawley, Nicola; He, Jiang; Heavner, Ben; Heckbert, Susan; Hernandez, Ryan; Herrington, David; Hersh, Craig; Hidalgo, Bertha; Hixson, James; Hokanson, John; Hong, Elliott; Hoth, Karin; Hsiung, Chao (Agnes); Huston, Haley; Hwu, Chii Min; Irvin, Marguerite; Jackson, Rebecca; Jain, Deepti; Jaquish, Cashell; Jhun, Min A; Johnsen, Jill; Johnson, Andrew; Johnson, Craig; Johnston, Rich; Jones, Kimberly; Kang, Hyun Min; Kaplan, Robert; Kardia, Sharon; Kathiresan, Sekar; Kaufman, Laura; Kelly, Shannon; Kenny, Eimear; Kessler, Michael; Khan, Alyna; Kinney, Greg; Konkle, Barbara; Kooperberg, Charles; Kramer, Holly; Krauter, Stephanie; Lange, Christoph; Lange, Ethan; Lange, Leslie; Laurie, Cathy; Laurie, Cecelia; LeBoff, Meryl; Lee, Seunggeun; Lee, Wen-Jane; LeFaive, Jonathon; Levine, David; Levy, Dan; Lewis, Joshua; Li, Yun; Lin, Honghuang; Lin, Keng Han; Liu, Simin; Liu, Yongmei; Loos, Ruth; Lunetta, Kathryn; Luo, James; Mahaney, Michael; Make, Barry; Manichaikul, Ani; Manson, JoAnn; Margolin, Lauren; Martin, Lisa; Mathai, Susan; Mathias, Rasika; McArdle, Patrick; McDonald, Merry-Lynn; McFarland, Sean; McGarvey, Stephen; Mei, Hao; Meyers, Deborah; Mikulla, Julie; Min, Nancy; Minear, Mollie; Minster, Ryan L; Mitchell, Braxton; Musani, Solomon; Mwasongwe, Stanford; Mychaleckyj, Josyf C; Nadkarni, Girish; Naik, Rakhi Johns; Natarajan, Pradeep; Nekhai, Sergei; Nickerson, Deborah; North, Kari; O'Connell, Jeff; O'Connor, Tim; Heather, Ochs-Balcom; Pankow, James; Papanicolaou, George; Parker, Margaret; Parsa, Afshin; Pattison, Jessica Tangarone; Penchev, Sara; Peralta, Juan Manuel; Perez, Marco; Perry, James; Peters, Ulrike; Peyser, Patricia; Phillips, Larry; Phillips, Sam; Pollin, Toni; Post, Wendy; Becker, Julia Powers; Boorgula, Meher Preethi; Preuss, Michael; Prokopenko, Dmitry; Psaty, Bruce; Qasba, Pankaj; Qiao, Dandi; Qin, Zhaohui; Rafaels, Nicholas; Raffield, Laura; Ramachandran, Vasan; Rao, D.C.; Rasmussen-Torvik, Laura; Ratan, Aakrosh; Redline, Susan; Reed, Robert; Regan, Elizabeth; Reiner, Alex; Rice, Ken; Rich, Stephen; Roden, Dan; Roselli, Carolina; Rotter, Jerome; Ruczinski, Ingo; Russell, Pamela; Ruuska, Sarah; Ryan, Kathleen; Sakornsakolpat, Phuwanat; Salimi, Shabnam; Salzberg, Steven; Sandow, Kevin; Sankaran, Vijay; Scheller, Christopher; Schmidt, Ellen; Schwander, Karen; Schwartz, David; Sciurba, Frank; Seidman, Christine; Sheehan, Vivien; Shetty, Amol; Shetty, Aniket; Hui-Heng Sheu, Wayne; Benjamin Shoemaker, M.; Silver, Brian; Silverman, Edwin; Smith, Jennifer; Smith, Josh; Smith, Nicholas; Smith, Tanja; Smoller, Sylvia; Snively, Beverly; Sofer, Tamar; Sotoodehnia, Nona; Stilp, Adrienne; Streeten, Elizabeth; Sung, Yun Ju; Sylvia, Jody; Szpiro, Adam; Sztalryd, Carole; Taliun, Daniel; Tang, Hua; Taub, Margaret; Taylor, Kent; Taylor, Simeon; Telen, Marilyn; Thornton, Timothy A.; Tinker, Lesley; Tirschwell, David; Tiwari, Hemant; Tracy, Russell; Tsai, Michael; Vaidya, Dhananjay; VandeHaar, Peter; Vrieze, Scott; Walker, Tarik; Wallace, Robert; Walts, Avram; Wan, Emily; Fei Wang, Fei; Watson, Karol; Weeks, Daniel E.; Weir, Bruce; Weiss, Scott; Weng, Lu-Chen; Willer, Cristen; Williams, Kayleen; Keoki Williams, L.; Wilson, Carla; Wilson, James; Wong, Quenna; Xu, Huichun; Yanek, Lisa; Yang, Ivana; Yang, Rongze; Zaghloul, Norann; Zhang, Yingze; Zhao, Snow Xueyan; Zhao, Wei; Zheng, Xiuwen; Zhi, Degui; Zhou, Xiang; Zody, Michael; Zoellner, Sebastian;
• Is Part Of: Circulation. Volume 138:Issue 13(2018)
• Publication Date: 2018-09-25
• Subjects: cholesterol, LDL -- chromosome mapping -- founder effect -- genetics -- pseudogenes; Blood -- Circulation -- Periodicals; Cardiovascular system -- Periodicals; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; 616.1
• DOI: 10.1161/CIRCULATIONAHA.118.034016
• Languages: English
• ISSNs: 0009-7322

Abstract

Abstract : Background: Elevated levels of low-density lipoprotein cholesterol (LDL-C) are a major risk factor for cardiovascular disease via its contribution to the development and progression of atherosclerotic lesions. Although the genetic basis of LDL-C has been studied extensively, currently known genetic variants account for only ≈20% of the variation in LDL-C levels. Methods: Through an array-based association analysis in 1102 Amish subjects, we identified a variant strongly associated with LDL-C levels. Using a combination of genetic analyses, zebrafish models, and in vitro experiments, we sought to identify the causal gene driving this association. Results: We identified a founder haplotype associated with a 15 mg/dL increase in LDL-C on chromosome 5. After recombination mapping, the associated region contained 8 candidate genes. Using a zebrafish model to evaluate the relevance of these genes to cholesterol metabolism, we found that expression of the transcribed pseudogene, APOOP1, increased LDL-C and vascular plaque formation. Conclusions: Based on these data, we propose that APOOP1 regulates levels of LDL-C in humans, thus identifying a novel mechanism of lipid homeostasis. Abstract : Supplemental Digital Content is available in the text.