Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
Natarajan, Pradeep; Pampana, Akhil; Graham, Sarah E.; Ruotsalainen, Sanni E.; Perry, James A.; de Vries, Paul S.; Broome, Jai G.; Pirruccello, James P.; Honigbere, Michael C.; Aragam, Krishna; Wolford, Brooke; Brody, Jennifer A.; Antonacci-Fulton, Lucinda; Arden, Moscati; Aslibekyan, Stella; Assimes, Themistocles L.; Ballantyne, Christie M.; Bielak, Lawrence F.; Bisl, Joshua C.; Cade, Brian E.; Do, Ron; Doddapaneni, Harsha; Emery, Leslie S.; Hung, Yi-Jen; Irvin, Marguerite R.; Khan, Alyna T.; Lange, Leslie; Lee, Jiwon; Lemaitre, Rozenn N.; Martin, Lisa W.; Metcalf, Ginger; Montasser, May E.; Moon, Jee-Young; Muzny, Donna; Connell, Jeffrey R. O.; Palmer, Nicholette D.; Peralta, Juan M.; Peyser, Patricia A.; Stilp, Adrienne M.; Tsai, Michael; Wang, Fei Fei; Weeks, Daniel E.; Yanek, Lisa R.; Wilson, James G.; Abecasis, Goncalo; Arnett, Donna K.; Becker, Lewis C.; Blangercy, John; Boerwinkle, Eric; Bowden, Donald W.; Chang, Yi-Cheng; Chen, Yii-Der, I; Choi, Won Jung; Correa, Adolfo; Curran, Joanne E.; Daly, Mark J.; DutcherE, Susan K.; Ellinor, Patrick T.; Fornage, Myriam; Freedman, Barry, I; Gabriel, Stacey; Germer, Soren; Gibbs, Richard A.; He, Jiang; Hveem, Kristian; Jarvik, Gail P.; Kaplan, Robert C.; Kardia, Sharon L. R.; Kennyn, Eimear; Kim, Ryan W.; Kooperberg, Charles; Laurie, Cathy C.; Lee, Seonwook; Lloyd-Jones, Don M.; Loos, Ruth J. F.; Lubitz, Steven A.; Mathias, Rasika A.; Martinez, Karine A. Viaud; McGarvey, Stephen T.; Mitche, Braxton D.; Nickerson, Deborah A.; North, Kari E.; Palotie, Aarno; Park, Cheol Joo; Psat, Bruce M. Y.; Rao, D. C.; Redline, Susan; Reiner, Alexander P.; Seo, Daekwan; Seo, Jeong-Sun; Smith, Albert, V; Tracy, Russell P.; Kathiresan, Sekar; Cupples, L. Adrienne; Rotten, Jerome, I; Morrison, Alanna C.; Rich, Stephen S.; Ripatti, Samuli; Wilier, Cristen; Peloso, Gina M.; Vasan, Ramachandran S.; Abe, Namiko; Albert, Christine; Almasy, Laura; Alonso, Alvaro; Ament, Seth; Anderson, Peter; Applebaum-Bowden, Deborah; Arking, Dan; Ashley-Koch, Allison; Auer, Paul; Avramopoulos, Dimitrios; Barnard, John; Barnes, Kathleen; Barr, R. Graham; Barron-Casella, Emily; Beaty, Terri; Becker, Diane; Beer, Rebecca; Begum, Ferdouse; Beitelshees, Amber; Benjamin, Emelia; Bezerra, Marcos; Bielak, Larry; Blackwel, Thomas; Bowler, Russell; Broecke, Ulrich; Bunting, Karen; Burchard, Esteban; Buth, Erin; Cardwel, Jonathan; Carty, Cara; Casaburi, Richard; Casella, James; Chaffin, Mark; Chang, Christy; Chasman, Daniel; Chavan, Sameer; Chen, Bo-Juen; Chen, Wei-Min; Chol, Michael; Choi, Seung Hoan; Chuang, Lee-Ming; Chung, Mina; Conomos, Matthew P.; Cornell, Elaine; Crapo, James; Curtis, Jeffrey; Custer, Brian; Damcott, Coleen; Darbar, Dawood; Das, Sayantan; David, Sean; Davis, Colleen; Daya, Michelle; de Andrade, Mariza; DeBaunuo, Michael; Duan, Qing; Devine, Ranjan Deka Dawn DeMeo Scott; Duggirala, Qing Ravi; Durda, Jon Peter; Dutcher, Susan; Eaton, Charles; Ekunwe, Lynette; Farber, Charles; Farnaml, Leanna; Fingerlin, Tasha; Flickinger, Matthew; Franceschini, Nora; Fu, Mao; Fullerton, Stephanie M.; Fulton, Lucinda; Gan, Weiniu; Gao, Yan; Gass, Margery; Ge, Bruce; Geng, Xiaoqi Priscilla; Germer, Soren; Gignoux, Chris; Gladwin, Mark; Glahn, David; Gogarten, Stephanie; Gong, Da-Wei; Goring, Harald; Gu, C. Charles; Guan, Yue; Guo, Xiuqing; Haessler, Jeff; Hall, Michael; Harris, Daniel; Hawle, Nicola Y.; 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; Jackson, Rebecca; Jain, Deepti; Jaquish, Cashell; Jhun, Min A.; Johnsen, Jill; Johnson, Andrew; Johnson, Craig; Johnston, Rich; Jones, Kimberly; Kang, Hyun Min; Kaufman, Laura; Kell, Shannon Y.; Kessler, Michael; Kinney, Greg; Konkle, Barbara; Kramer, Holly; Krauter, Stephanie; Lange, Christoph; Lange, Ethan; Laurie, Cecelia; LeBoff, Meryl; Lee, Seunggeun Shawn; Lee, Wen-Jane; LeFaive, Jonathon; Levine, David; Levy, Dan; Lewis, Joshua; Li, Yun; Lin, Honghuang; Lin, Keng Han; Lin, Xihong; Liu, Simin; Liu, Yongmei; Lunetta, Kathryn; Luo, James; Mahaney, Michael; Make, Barry; Manichaikul, Ani; Mansonl, JoAnn; Margolin, Lauren; Mathai, Susan; McArdle, Patrick; Mcdonald, Merry-Lynn; McFarland, Sean; McHugh, Caitlin; Mei, Hao; Meyers, Deborah A.; Mikulla, Julie; Min, Nancy; Minear, Mollie; Minster, Ryan L.; Musani, Solomon; Mwasongwe, Stanford; Mychaleckyj, Josyf C.; Nadkarni, Girish; Naik, Rakhi; Naseri, Take; Nekhai, Sergei; Nelson, Sarah C.; Nickerson, Deborah; Connell, Jeff O.; Connor, Tim O.; Ochs-Balcom, Heather; Pankow, James; Papanicolaou, George; Parkerl, Margaret; Parsa, Afshin; Penchey, Sara; Perez, Marco; Peters, Ulrike; Phillips, Lawrence S.; Phillips, Sam; Pollin, Toni; Post, Wendy; Becker, Julia Powers; Boorgula, Meher Preethi; Preuss, Michael; Prokopenko, Dmitry; Qasba, Pankaj; Qiao, Dandi; Rafaels, Nicholas; Raffield, Laura; Rasmussen-Torvik, Laura; Ratan, Aakrosh; Reed, Robert; Reganl, Elizabeth; Reupena, Muagututi Sefuiva; Rice, Ken; Roden, Dan; Roselli, Carolina; Ruczinski, Ingo; Russel, Pamela; Ruuska, Sarah; Ryan, Kathleen; Sabino, Ester Cerdeira; Sakornsakolpatl, Phuwanat; Salzberg, Steven; Sandow, Kevin; Sankaran, Vijay G.; Scheller, Christopher; Schmidt, Ellen; Schwander, Karen; Schwartz, David; Sciurba, Frank; Seidman, Christine; Seidman, Jonathan; Sheehan, Vivien; Shetty, Amol; Shetty, Aniket; Sheu, Wayne Hui-Heng; Shoemaker, M. Benjamin; Silver, Brian; Silvermanl, Edwin; Smith, Jennifer; Smith, Josh; Smith, Nicholas; Smith, Tanja; Smoller, Sylvia; Snively, Beverly; Soferlm, Tamar; Streeten, Elizabeth; Su, Jessica Lasky; Sung, Yun Ju; Sylvia, Jody; Sztalryd, Carole; Taliun, Daniel; Tang, Hua; Taub, Margaret; Taylor, Kent D.; Taylor, Simeon; Telen, Marilyn; Thornton, Timothy A.; Tinker, Lesley; Tirschwel, David; Tiwari, Hemant; Vaidya, Dhananjay; VandeHaar, Peter; Vrieze, Scott; Walker, Tarik; Wallace, Robert; Waits, Avram; Wan, Emily; Wang, Heming; Watson, Karol; Weir, Bruce; Weiss, Scott; Weng, Lu-Chen; Williams, Kayleen; Williams, L. Keoki; Wilson, Carla; Wong, Quenna; Xu, Huichun; Yang, Ivana; Yang, Rongze; Zaghlou, Norann; Zekavat, Maryam; Zhang, Yingze; Zhao, Snow Xueyan; Zhao, Wei; Zni, Degui; Zhou, Xiang; Zhu, Xiaofeng; Zody, Michael; Zoellner, Sebastian; Palotie, Aarno; Daly, Mark; Jacob, Howard; Matakidou, Athena; Runz, Heiko; John, Sally; Plenge, Robert; McCarthy, Mark; Hunkapiller, Julie; Ehm, Meg; Waterworth, Dawn; Fox, Caroline; Malarstig, Anders; Klinger, Kathy; Call, Kathy; Mkel, Tomi; Kaprio, Jaakko; Virolainen, Petri; Pulkki, Kari; Kilpi, Terhi; Perola, Markus; Partanen, Jukka; Pitkranta, Anne; Kaarteenaho, Riitta; Vainio, Seppo; Savinainen, Kimmo; Kosma, Veli-Matti; Kujala, Urho; Tuovila, Outi; Hendolin, Minna; Pakkanen, Raimo; Waring, Jeff; Riley-Gillis, Bridget; Liu, Jimmy; Biswas, Shameek; Diogo, Dorothee; Marshall, Catherine; Hu, Xinli; Gossel, Matthias; Ripatti, Samuli; Schleutker, Johanna; Arvas, Mikko; Hinttala, Reetta; Kettunen, Johannes; Laaksonen, Reijo; Mannermaa, Arto; Paloneva, Juha; Soininen, Hilkka; Julkunen, Valtteri; Remes, Anne; Klviinen, Reetta; Hiltunen, Mikko; Peltola, Jukka; Tienari, Pentti; Rinne, Juha; Ziemann, Adam; Waring, Jeffrey; Esmaeeli, Sahar; Smaoui, Nizar; Lehtonen, Anne; Eaton, Susan; Landenper, Sanni; Michon, John; Kerchner, Geoff; Bowers, Natalie; Teng, Edmond; Eicher, John; Mehta, Vinay; Gormle, Padhraig Y.; Linden, Kari; Whelan, Christopher; Xu, Fanli; Pulford, David; Frkkil, Martti; Pikkarainen, Sampsa; Jussila, Airi; Blomster, Timo; Kiviniemi, Mikko; Voutilainen, Markku; Georgantas, Bob; Heap, Graham; Rahimov, Fedik; Usiskin, Keith; Maranville, Joseph; Lu, Tim; Oh, Danny; Kalpala, Kirsi; Miller, Melissa; McCarthy, Linda; Eklund, Kari; Palomki, Antti; Isomki, Pia; Piri, Laura; Kaipiainen-Seppnen, Oili; Lertratanaku, Apinya; Bing, David Close Marla Hochfeld Nan; Gordillo, Jorge Esparza; Mars, Nina; Laitinen, Tarja; Pelkonen, Margit; Kauppi, Paula; Kankaanranta, Hannu; Harju, Terttu; Greenberg, Steven; Chen, Hubert; Betts, Jo; Ghosh, Soumitra; Salomaa, Veikko; Niiranen, Teemu; Juonala, Markus; Metsrinne, Kaj; Khnen, Mika; Junttila, Juhani; Laakso, Markku; Pihlajamki, Jussi; Sinisalo, Juha; Taskinen, Marja-Riitta; Tuomi, Tiinamaija; Laukkanen, Jari; Challis, Ben; Peterson, Andrew; Chu, Audrey; Parkkinen, Jaakko; Muslin, Anthony; Joensuu, Heikki; Meretoja, Tuomo; Aaltonen, Lauri; Auranen, Annika; Karihtala, Peeter; Kauppila, Saila; Auvinen, Pivi; Elenius, Klaus; Popovic, Relja; Schutzman, Jennifer; Loboda, Andrey; Chhibber, Aparna; Lehtonen, Heli; McDonough, Stefan; Crohns, Marika; Kulkarni, Diptee; Kaarniranta, Kai; Turunen, Joni; Ollila, Terhi; Seitsonen, Sanna; Uusitalo, Hannu; Aaltonen, Vesa; Uusitalo-Jrvinen, Hannele; Luodonp, Marja; Hautala, Nina; Strauss, Erich; Chen, Hao; Podgornaia, Anna; Hoffman, Joshua; Tasanen, Kaisa; Huilaja, Laura; Hannula-Jouppi, Katariina; Salmi, Teea; Peltonen, Sirkku; Koulu, Leena; Harvima, Ilkka; Wu, Ying; Choy, David; Jalanko, Anu; Kajanne, Risto; Lyhs, Ulrike; Kaunisto, Mari; Davis, Justin Wade; Quarless, Danjuma; Petrovski, Slav; Chen, Chia-Yen; Bronson, Paola; Yang, Robert; Chang, Diana; Bhangale, Tushar; Holzinger, Emily; Wang, Xulong; Chen, Xing; Auro, Kirsi; Wang, Clarence; Xu, Ethan; Auge, Franck; Chatelain, Clement; Kurki, Mitja; Karjalainen, Juha; Havulinna, Aki; Palin, Kimmo; Palta, Priit; Parolo, Pietro Della Briotta; Zhou, Wei; Lemmel, Susanna; Rivas, Manuel; Harju, Jarmo; Lehisto, Arto; Ganna, Andrea; Llorens, Vincent; Karlsson, Antti; Kristiansson, Kati; Hyvrinen, Kati; Ritari, Jarmo; Wahlfors, Tiina; Koskinen, Miika; Pylkäs, Katri; Kalaoja, Marita; Karjalainen, Minna; Mantere, Tuomo; Kangasniemi, Eeva; Heikkinen, Sami; Laakkonen, Eija; Kononen, Juha; Loukola, Anu; Laiho, Pivi; Sistonen, Tuuli; Kaiharju, Essi; Laukkanen, Markku; Jrvensivu, Elina; Lhteenmki, Sini; Mnnikk, Lotta; Wong, Regis; Mattsson, Hannele; Hiekkalinna, Tero; Jimnez, Manuel Gonzlez; Donner, Kati; Prn, KaIle; Nunez-Fontarnau, Javier; Kilpelinen, Elina; Sipi, Timo P.; Brein, Georg; Dada, Alexander; Awaisa, Ghazal; Shcherban, Anastasia; Sipil, Tuomas; Laivuori, Hannele; Kiiskinen, Tuomo; Siirtola, Harri; Tabuenca, Javier Gracia; Kallio, Lila; Soini, Sirpa; Pitknen, Kimmo; Kuopio, Teijo (2021-04-12)
Springer Nature
12.04.2021
Natarajan, P., Pampana, A., Graham, S.E. et al. Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices. Nat Commun 12, 2182 (2021). https://doi.org/10.1038/s41467-021-22339-1
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© The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
https://creativecommons.org/licenses/by/4.0/
© The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi-fe2022040627379
https://urn.fi/URN:NBN:fi-fe2022040627379
Tiivistelmä
Abstract
Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids.
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