University of Oulu

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

Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices

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Author: Natarajan, Pradeep1,2,3; Pampana, Akhil1,2; Graham, Sarah E.4;
Ruotsalainen, Sanni E.5; Perry, James A.6; de Vries, Paul S.7; Broome, Jai G.8; Pirruccello, James P.1,2,3; Honigbere, Michael C.2,3; Aragam, Krishna1,2,3; Wolford, Brooke9; Brody, Jennifer A.1; Antonacci-Fulton, Lucinda10,11; Arden, Moscati12; Aslibekyan, Stella13; Assimes, Themistocles L.14,15; Ballantyne, Christie M.16,17; Bielak, Lawrence F.18; Bisl, Joshua C.19; Cade, Brian E.20; Do, Ron12; Doddapaneni, Harsha21; Emery, Leslie S.8; Hung, Yi-Jen22; Irvin, Marguerite R.13; Khan, Alyna T.8; Lange, Leslie23; Lee, Jiwon20; Lemaitre, Rozenn N.19; Martin, Lisa W.2,24; Metcalf, Ginger21; Montasser, May E.6; Moon, Jee-Young25; Muzny, Donna21; Connell, Jeffrey R. O.6; Palmer, Nicholette D.26; Peralta, Juan M.27; Peyser, Patricia A.18; Stilp, Adrienne M.8; Tsai, Michael28; Wang, Fei Fei8; Weeks, Daniel E.29; Yanek, Lisa R.30; Wilson, James G.31,32; Abecasis, Goncalo33; Arnett, Donna K.34; Becker, Lewis C.30; Blangercy, John27; Boerwinkle, Eric7,21; Bowden, Donald W.26; Chang, Yi-Cheng35; Chen, Yii-Der, I36; Choi, Won Jung37; Correa, Adolfo38; Curran, Joanne E.27; Daly, Mark J.39; DutcherE, Susan K.10,11; Ellinor, Patrick T.2,40; Fornage, Myriam41; Freedman, Barry, I42; Gabriel, Stacey43; Germer, Soren44; Gibbs, Richard A.21,45; He, Jiang46; Hveem, Kristian47,48; Jarvik, Gail P.49; Kaplan, Robert C.25,50; Kardia, Sharon L. R.18; Kennyn, Eimear12; Kim, Ryan W.37; Kooperberg, Charles50; Laurie, Cathy C.8; Lee, Seonwook37; Lloyd-Jones, Don M.51; Loos, Ruth J. F.12,52; Lubitz, Steven A.40; Mathias, Rasika A.30; Martinez, Karine A. Viaud53; McGarvey, Stephen T.54; Mitche, Braxton D.6,55; Nickerson, Deborah A.56,57; North, Kari E.58; Palotie, Aarno2,5,39,59; Park, Cheol Joo37; Psat, Bruce M. Y.19,60,61; Rao, D. C.62; Redline, Susan20; Reiner, Alexander P.50; Seo, Daekwan37; Seo, Jeong-Sun37; Smith, Albert, V33,63; Tracy, Russell P.64; Kathiresan, Sekar2,3,65,66; Cupples, L. Adrienne67,68; Rotten, Jerome, I36; Morrison, Alanna C.7; Rich, Stephen S.69; Ripatti, Samuli2,5,70,59; Wilier, Cristen4,9,71; Peloso, Gina M.68; Vasan, Ramachandran S.72,73,67; Abe, Namiko44; Albert, Christine74; Almasy, Laura75; Alonso, Alvaro76; Ament, Seth77; Anderson, Peter78,79; Applebaum-Bowden, Deborah80; Arking, Dan81; Ashley-Koch, Allison82; Auer, Paul83; Avramopoulos, Dimitrios81; Barnard, John84; Barnes, Kathleen85; Barr, R. Graham86; Barron-Casella, Emily81; Beaty, Terri81; Becker, Diane87; Beer, Rebecca88; Begum, Ferdouse81; Beitelshees, Amber77; Benjamin, Emelia89; Bezerra, Marcos90; Bielak, Larry91; Blackwel, Thomas91; Bowler, Russell92; Broecke, Ulrich93; Bunting, Karen44; Burchard, Esteban94; Buth, Erin95; Cardwel, Jonathan85; Carty, Cara96; Casaburi, Richard97; Casella, James81; Chaffin, Mark98; Chang, Christy77; Chasman, Daniel99; Chavan, Sameer85; Chen, Bo-Juen44; Chen, Wei-Min100; Chol, Michael101; Choi, Seung Hoan98; Chuang, Lee-Ming102; Chung, Mina103; Conomos, Matthew P.85; Cornell, Elaine104; Crapo, James99; Curtis, Jeffrey91; Custer, Brian105; Damcott, Coleen77; Darbar, Dawood106; Das, Sayantan91; David, Sean90; Davis, Colleen78; Daya, Michelle85; de Andrade, Mariza107; DeBaunuo, Michael90; Duan, Qing56; Devine, Ranjan Deka Dawn DeMeo Scott77; Duggirala, Qing Ravi108; Durda, Jon Peter104; Dutcher, Susan78; Eaton, Charles67; Ekunwe, Lynette79; Farber, Charles100; Farnaml, Leanna101; Fingerlin, Tasha109; Flickinger, Matthew91; Franceschini, Nora110; Fu, Mao77; Fullerton, Stephanie M.79; Fulton, Lucinda10,11,78; Gan, Weiniu88; Gao, Yan79; Gass, Margery90; Ge, Bruce89; Geng, Xiaoqi Priscilla91; Germer, Soren44; Gignoux, Chris78; Gladwin, Mark79; Glahn, David111; Gogarten, Stephanie78; Gong, Da-Wei77; Goring, Harald98; Gu, C. Charles78; Guan, Yue77; Guo, Xiuqing112; Haessler, Jeff113; Hall, Michael79; Harris, Daniel77; Hawle, Nicola Y.111; Heavner, Ben95; Heckbert, Susan78; Hernandez, Ryan114; Herrington, David115; Hersh, Craig116; Hidalgo, Bertha56; Hixson, James117; Hokanson, John85; Hong, Elliott77; Hoth, Karin118; Hsiung, Chao Agnes119; Huston, Haley120; Hwu, Chii Min121; Jackson, Rebecca122; Jain, Deepti78; Jaquish, Cashell88; Jhun, Min A.91; Johnsen, Jill123; Johnson, Andrew88; Johnson, Craig78; Johnston, Rich76; Jones, Kimberly81; Kang, Hyun Min78; Kaufman, Laura101; Kell, Shannon Y.105; Kessler, Michael77; Kinney, Greg85; Konkle, Barbara90; Kramer, Holly124; Krauter, Stephanie78; Lange, Christoph57; Lange, Ethan85; Laurie, Cecelia78; LeBoff, Meryl101; Lee, Seunggeun Shawn91; Lee, Wen-Jane121; LeFaive, Jonathon91; Levine, David78; Levy, Dan88; Lewis, Joshua77; Li, Yun88; Lin, Honghuang65; Lin, Keng Han91; Lin, Xihong91; Liu, Simin90; Liu, Yongmei57; Lunetta, Kathryn82; Luo, James88; Mahaney, Michael47; Make, Barry81; Manichaikul, Ani100; Mansonl, JoAnn125; Margolin, Lauren98; Mathai, Susan85; McArdle, Patrick77; Mcdonald, Merry-Lynn81; McFarland, Sean79; McHugh, Caitlin46; Mei, Hao79; Meyers, Deborah A.126; Mikulla, Julie88; Min, Nancy79; Minear, Mollie88; Minster, Ryan L.81; Musani, Solomon127; Mwasongwe, Stanford79; Mychaleckyj, Josyf C.100; Nadkarni, Girish100; Naik, Rakhi81; Naseri, Take128; Nekhai, Sergei129; Nelson, Sarah C.95; Nickerson, Deborah56,57,78; Connell, Jeff O.79; Connor, Tim O.77; Ochs-Balcom, Heather130; Pankow, James131; Papanicolaou, George88; Parkerl, Margaret101; Parsa, Afshin77; Penchey, Sara77; Perez, Marco132; Peters, Ulrike132; Phillips, Lawrence S.76; Phillips, Sam78; Pollin, Toni77; Post, Wendy133; Becker, Julia Powers134; Boorgula, Meher Preethi85; Preuss, Michael65; Prokopenko, Dmitry65; Qasba, Pankaj88; Qiao, Dandi101; Rafaels, Nicholas85; Raffield, Laura135; Rasmussen-Torvik, Laura136; Ratan, Aakrosh100; Reed, Robert77; Reganl, Elizabeth137; Reupena, Muagututi Sefuiva137; Rice, Ken78; Roden, Dan138; Roselli, Carolina98; Ruczinski, Ingo81; Russel, Pamela59; Ruuska, Sarah57; Ryan, Kathleen77; Sabino, Ester Cerdeira139; Sakornsakolpatl, Phuwanat73; Salzberg, Steven81; Sandow, Kevin140; Sankaran, Vijay G.141; Scheller, Christopher91; Schmidt, Ellen91; Schwander, Karen78; Schwartz, David85; Sciurba, Frank78; Seidman, Christine142; Seidman, Jonathan79; Sheehan, Vivien143; Shetty, Amol77; Shetty, Aniket85; Sheu, Wayne Hui-Heng121; Shoemaker, M. Benjamin144; Silver, Brian145; Silvermanl, Edwin101; Smith, Jennifer91; Smith, Josh78; Smith, Nicholas146; Smith, Tanja44; Smoller, Sylvia147; Snively, Beverly148; Soferlm, Tamar85; Streeten, Elizabeth77; Su, Jessica Lasky85; Sung, Yun Ju78; Sylvia, Jody101; Sztalryd, Carole77; Taliun, Daniel91; Tang, Hua99; Taub, Margaret81; Taylor, Kent D.149; Taylor, Simeon77; Telen, Marilyn82; Thornton, Timothy A.78; Tinker, Lesley96; Tirschwel, David149; Tiwari, Hemant88; Vaidya, Dhananjay81; VandeHaar, Peter91; Vrieze, Scott150; Walker, Tarik85; Wallace, Robert118; Waits, Avram85; Wan, Emily101; Wang, Heming151; Watson, Karol97; Weir, Bruce78; Weiss, Scott101; Weng, Lu-Chen90; Williams, Kayleen78; Williams, L. Keoki152; Wilson, Carla101; Wong, Quenna78; Xu, Huichun77; Yang, Ivana85; Yang, Rongze77; Zaghlou, Norann77; Zekavat, Maryam98; Zhang, Yingze90; Zhao, Snow Xueyan91; Zhao, Wei91; Zni, Degui117; Zhou, Xiang91; Zhu, Xiaofeng103; Zody, Michael44; Zoellner, Sebastian9; Palotie, Aarno2,5,39,59; Daly, Mark39,59; Jacob, Howard153; Matakidou, Athena154; Runz, Heiko155; John, Sally155; Plenge, Robert156; McCarthy, Mark157; Hunkapiller, Julie157; Ehm, Meg158; Waterworth, Dawn158; Fox, Caroline159; Malarstig, Anders160; Klinger, Kathy161; Call, Kathy161; Mkel, Tomi162; Kaprio, Jaakko163; Virolainen, Petri164; Pulkki, Kari164; Kilpi, Terhi165; Perola, Markus165; Partanen, Jukka166; Pitkranta, Anne167; Kaarteenaho, Riitta168; Vainio, Seppo168; Savinainen, Kimmo169; Kosma, Veli-Matti170; Kujala, Urho171; Tuovila, Outi172; Hendolin, Minna172; Pakkanen, Raimo172; Waring, Jeff153; Riley-Gillis, Bridget153; Liu, Jimmy155; Biswas, Shameek156; Diogo, Dorothee159; Marshall, Catherine160; Hu, Xinli160; Gossel, Matthias161; Ripatti, Samuli2,5,70,59; Schleutker, Johanna164; Arvas, Mikko166; Hinttala, Reetta168; Kettunen, Johannes168; Laaksonen, Reijo169; Mannermaa, Arto170; Paloneva, Juha171; Soininen, Hilkka172; Julkunen, Valtteri173; Remes, Anne174; Klviinen, Reetta173; Hiltunen, Mikko173; Peltola, Jukka175; Tienari, Pentti175; Rinne, Juha176; Ziemann, Adam153; Waring, Jeffrey153; Esmaeeli, Sahar153; Smaoui, Nizar153; Lehtonen, Anne153; Eaton, Susan155; Landenper, Sanni155; Michon, John157; Kerchner, Geoff157; Bowers, Natalie157; Teng, Edmond157; Eicher, John159; Mehta, Vinay159; Gormle, Padhraig Y.159; Linden, Kari160; Whelan, Christopher160; Xu, Fanli158; Pulford, David158; Frkkil, Martti167; Pikkarainen, Sampsa167; Jussila, Airi175; Blomster, Timo174; Kiviniemi, Mikko173; Voutilainen, Markku176; Georgantas, Bob153; Heap, Graham153; Rahimov, Fedik153; Usiskin, Keith156; Maranville, Joseph156; Lu, Tim157; Oh, Danny157; Kalpala, Kirsi160; Miller, Melissa160; McCarthy, Linda158; Eklund, Kari167; Palomki, Antti176; Isomki, Pia175; Piri, Laura176; Kaipiainen-Seppnen, Oili154,156,173,174; Lertratanaku, Apinya153; Bing, David Close Marla Hochfeld Nan160; Gordillo, Jorge Esparza158; Mars, Nina158; Laitinen, Tarja175; Pelkonen, Margit173; Kauppi, Paula167; Kankaanranta, Hannu175; Harju, Terttu174; Greenberg, Steven156; Chen, Hubert157; Betts, Jo158; Ghosh, Soumitra158; Salomaa, Veikko177; Niiranen, Teemu177; Juonala, Markus176; Metsrinne, Kaj176; Khnen, Mika175; Junttila, Juhani174; Laakso, Markku173; Pihlajamki, Jussi173; Sinisalo, Juha167; Taskinen, Marja-Riitta167; Tuomi, Tiinamaija167; Laukkanen, Jari178; Challis, Ben154; Peterson, Andrew157; Chu, Audrey159; Parkkinen, Jaakko160; Muslin, Anthony161; Joensuu, Heikki167; Meretoja, Tuomo167; Aaltonen, Lauri167; Auranen, Annika170; Karihtala, Peeter174; Kauppila, Saila174; Auvinen, Pivi173; Elenius, Klaus176; Popovic, Relja153; Schutzman, Jennifer157; Loboda, Andrey159; Chhibber, Aparna159; Lehtonen, Heli160; McDonough, Stefan160; Crohns, Marika161; Kulkarni, Diptee158; Kaarniranta, Kai173; Turunen, Joni167; Ollila, Terhi167; Seitsonen, Sanna167; Uusitalo, Hannu175; Aaltonen, Vesa176; Uusitalo-Jrvinen, Hannele175; Luodonp, Marja174; Hautala, Nina174; Strauss, Erich157; Chen, Hao157; Podgornaia, Anna159; Hoffman, Joshua158; Tasanen, Kaisa174; Huilaja, Laura174; Hannula-Jouppi, Katariina167; Salmi, Teea175; Peltonen, Sirkku176; Koulu, Leena176; Harvima, Ilkka173; Wu, Ying160; Choy, David157; Jalanko, Anu59; Kajanne, Risto59; Lyhs, Ulrike59; Kaunisto, Mari59; Davis, Justin Wade153; Quarless, Danjuma153; Petrovski, Slav154; Chen, Chia-Yen155; Bronson, Paola155; Yang, Robert156; Chang, Diana157; Bhangale, Tushar157; Holzinger, Emily159; Wang, Xulong159; Chen, Xing160; Auro, Kirsi158; Wang, Clarence161; Xu, Ethan161; Auge, Franck161; Chatelain, Clement161; Kurki, Mitja59; Karjalainen, Juha59; Havulinna, Aki59; Palin, Kimmo154; Palta, Priit59; Parolo, Pietro Della Briotta59; Zhou, Wei142; Lemmel, Susanna59; Rivas, Manuel136; Harju, Jarmo59; Lehisto, Arto59; Ganna, Andrea59; Llorens, Vincent59; Karlsson, Antti164; Kristiansson, Kati165; Hyvrinen, Kati166; Ritari, Jarmo166; Wahlfors, Tiina166; Koskinen, Miika179; Pylkäs, Katri168; Kalaoja, Marita168; Karjalainen, Minna168; Mantere, Tuomo168; Kangasniemi, Eeva169; Heikkinen, Sami170; Laakkonen, Eija171; Kononen, Juha171; Loukola, Anu167; Laiho, Pivi165; Sistonen, Tuuli165; Kaiharju, Essi165; Laukkanen, Markku165; Jrvensivu, Elina165; Lhteenmki, Sini165; Mnnikk, Lotta165; Wong, Regis165; Mattsson, Hannele165; Hiekkalinna, Tero165; Jimnez, Manuel Gonzlez165; Donner, Kati59; Prn, KaIle59; Nunez-Fontarnau, Javier59; Kilpelinen, Elina59; Sipi, Timo P.59; Brein, Georg59; Dada, Alexander59; Awaisa, Ghazal59; Shcherban, Anastasia59; Sipil, Tuomas59; Laivuori, Hannele59; Kiiskinen, Tuomo59; Siirtola, Harri158; Tabuenca, Javier Gracia158; Kallio, Lila180; Soini, Sirpa181; Pitknen, Kimmo182; Kuopio, Teijo183
Organizations: 1Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
2Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
3Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
4Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
5Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.
6Univ Maryland, Div Endocrinol, Diabet & Nutr & Program Personalized & Genom Med, Sch Med, Baltimore, MD USA.
7Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol Human Genet & Environm Sci, Human Genet Ctr, Sch Publ Hlth, Houston, TX 77030 USA.
8Univ Washington, Dept Biostat, Seattle, WA USA.
9Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI USA.
10Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO USA.
11Washington Univ, Dept Genet, St Louis, MO 63110 USA.
12Ichan Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY USA.
13Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL USA.
14Stanford Univ, Dept Med, Sch Med, Stanford, CA USA.
15VA Palo Alto Hlth Care Syst, Palo Alto, CA USA.
16Baylor Coll Med, Sect Cardiovasc Res, Houston, TX USA.
17Houston Methodist Debakey Heart & Vasc Ctr, Houston, TX USA.
18Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
19Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
20Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA.
21Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX USA.
22Triserv Gen Hosp, Div Endocrine & Metab, Songshan Branch, Taipei, Taiwan.
23Univ Colorado, Div Biomed Informat & Personalized Med, Dept Med, Anschutz Med Campus, Aurora, CO USA.
24George Washington Univ, Sch Med & Healthcare Sci, Div Cardiol, Washington, DC USA.
25Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
26Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA.
27Univ Texas Brownsville, Dept Human Genet & South Texas Diabet & Obes Inst, Rio Grande Valley Sch Med, Brownsville, TX USA.
28Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
29Univ Pittsburgh, Dept Human Genet & Biostat, Pittsburgh, PA USA.
30Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
31Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Boston, MA USA.
32Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
33Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
34Univ Kentucky, Sch Publ Hlth, Deans Off, Lexington, KY USA.
35Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan.
36Ucla Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, Lundquist Inst Biomed Innovat Harbor, Torrance, CA USA.
37Psomagen Inc, Rockville, MD USA.
38Univ Mississippi, Dept Med, Med Ctr, Jackson, MS USA.
39Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA.
40Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Cardiovasc Res Ctr, Boston, MA USA.
41Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA.
42Wake Forest Sch Med, Dept Internal Med, Sect Nephrol, Salem, NC USA.
43Broad Inst Harvard & MIT, Genom Platform, Cambridge, MA USA.
44New York Genome Ctr, New York, NY USA.
45Baylor Coll Med, Dept Mol & Human Genet, Houston, TX USA.
46Tulane Univ, Translat Sci Inst, Sch Publ Hlth, Dept Epidemiol, New Orleans, LA 70118 USA.
47Norwegian Univ Sci & Technol, Hunt Res Ctr, Dept Publ Hlth & Gen Practice, Levanger, Norway.
48Norwegian Univ Sci & Technol NTNU, Fac Med & Hlth Sci, KG Jebsen Ctr Genet Epidemiol, Dept Publ Hlth & Nursing, Trondheim, Norway.
49Univ Washington, Dept Med Med Genet, Seattle, WA USA.
50Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
51Northwestern Univ, Feinberg Sch Med, Prevent Med, Chicago, IL USA.
52Ichan Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY USA.
53Illumina Inc, IllUmina Lab Serv, San Diego, CA USA.
54Brown Univ, Dept Epidemiol, Int Hlth Inst, Providence, RI USA.
55Baltimore Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD USA.
56Univ Washington, Dept Genome Sci, Seattle, WA USA.
57Univ Washington, Ctr Mendelian Genom, Seattle, WA USA.
58Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
59Univ Helsinki, Inst Mol Med Finland, HiLIFE, Helsinki, Finland.
60Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
61Univ Washington, Dept Epidemiol, Seattle, WA USA.
62Washington Univ, Div Biostat, Sch Med, St Louis, MO USA.
63Iceland Heart Assoc, Kopavogur, Iceland.
64Univ Vermont, Larrner Coll Med, Dept Pathol & Lab Med, Colchester, VT USA.
65Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA.
66Verve Therapeut, Cambridge, MA USA.
67NHLBI Framingham Heart Study, Framingham, MA USA.
68Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
69Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
70Univ Helsinki, Fac Med, Dept Publ Hlth, Helsinki, Finland.
71Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
72Boston Univ, Dept Med, Sect Prevent Med & Epidemiol, Sch Med, Boston, MA USA.
73Boston Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA USA.
74Brigham & Womens Hosp, Cedars Sinai, 75 Francis St, Boston, MA 02115 USA.
75Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
76Emory Univ, Atlanta, GA 30322 USA.
77Univ Maryland, Baltimore, MD 21201 USA.
78Univ Washington, Seattle, WA 98195 USA.
79Univ Mississippi, Jackson, MS 39216 USA.
80NIH, Bldg 10, Bethesda, MD 20892 USA.
81Johns Hopkins Univ, Baltimore, MD USA.
82Duke Univ, Durham, NC USA.
83Univ Wisconsin, Milwaukee, WI 53201 USA.
84Cleveland Clin, Cleveland, OH 44106 USA.
85Univ Colorado, Denver, CO 80202 USA.
86Columbia Univ, New York, NY USA.
87Johns Hopkins Univ, Med, Baltimore, MD USA.
88NIH, NHLBI, Bethesda, MD USA.
89Boston Univ, Boston Univ Sch Med, Massachusetts Gen Hosp, Boston, MA USA.
90Fundacao Hematol & Hemoterapia Pernambuco Hemope, Recife, PE, Brazil.
91Womens Hlth Initiat, Seattle, WA USA.
92Natl Jewish Hlth, Denver, CO USA.
93Med Coll Wisconsin, Milwaukee, WI USA.
94Univ Calif San Francisco, San Francisco, CA 94143 USA.
95Univ Washington, Biostat, Seattle, WA USA.
96Univ Michigan, Ann Arbor, MI 48109 USA.
97Univ Calif Los Angeles, Los Angeles, CA USA.
98Broad Inst, Cambridge, MA USA.
99Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
100Univ Virginia, Charlottesville, VA USA.
101Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
102Natl Taiwan Univ, Taiwan Univ Hosp, Taipei, Taiwan.
103Case Western Reserve Univ, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA.
104Univ Vermont, Burlington, VT USA.
105Vitalant Res Inst, San Francisco, CA USA.
106Univ Illinois, Chicago, IL USA.
107Mayo Clin, Hlth Sci Res, Rochester, MN USA.
108Univ Texas Rio Grande Valley Sch Med, Edinburg, TX USA.
109Natl Jewish Hlth, Ctr Genes Environm & Hlth, Denver, CO USA.
110Univ N Carolina, Epidemiol, Chapel Hill, NC USA.
111Yale Univ, New Haven, CT USA.
112Lundquist Inst, Los Angeles, CA USA.
113Fred Hutchinson Canc Res Ctr, Womens Hlth Initiat, 1124 Columbia St, Seattle, WA 98104 USA.
114Univ Calif San Francisco, McGill Univ, San Francisco, CA 94143 USA.
115Wake Forest Baptist Hlth, Winston Salem, NC USA.
116Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
117Univ Texas Hlth Houston, Houston, TX USA.
118Univ Iowa, Iowa City, IA USA.
119Natl Hlth Res Inst Taiwan, Inst Populat Hlth Sci, Miaoli County, TW, Taiwan.
120Blood Works Northwest, Seattle, WA USA.
121Taichung Vet Gen Hosp Taiwan, Taichung, Taiwan.
122Ohio State Univ, Div Endocrinol Diabet & Metab, Wexner Med Ctr, Columbus, OH USA.
123Univ Washington, Blood Works Northwest, Seattle, WA 98195 USA.
124Loyola Univ Publ Hlth Sci, Maywood, IL USA.
125Brown Univ, Womens Hlth Initiat Epidemiol, Providence, RI 02912 USA.
126Univ Arizona, Tucson, AZ USA.
127Univ Mississippi, Med, Jackson, MS USA.
128Govt Samoa, Minist Hlth, Apia, WS, Samoa.
129Howard Univ, Washington, DC 20059 USA.
130Univ Buffalo, Buffalo, NY USA.
131Univ Minnesota, Minneapolis, MN USA.
132Univ Washington, Fred Hutchinson Canc Res, Seattle, WA 98195 USA.
133Johns Hopkins Univ, Cardiol Med, Baltimore, MD USA.
134Univ Colorado, Med, Denver, CO 80202 USA.
135Univ N Carolina, Genet, Chapel Hill, NC 27515 USA.
136Northwestern Univ, Chicago, IL 60611 USA.
137Lutia I Puava Ae Mapu I Fagalele, Apia, WS, Samoa.
138Vanderbilt Univ, Med Pharmacol Biomedicla Informat, 221 Kirkland Hall, Nashville, TN 37235 USA.
139Univ Sao Paulo, Fac Med, Sao Paulo, SP, Brazil.
140Lundquist Inst, TGPS, Torrance, CA USA.
141Harvard Med Sch, Broad Inst, Div Hematol Oncol, Boston, MA 02115 USA.
142Harvard Med Sch, Genet, Boston, MA USA.
143Baylor Coll Med, Pediat, Houston, TX 77030 USA.
144Vanderbilt Univ, Med Cardiol, 221 Kirkland Hall, Nashville, TN 37235 USA.
145UMass Mem Med Ctr, Worcester, MA USA.
146Univ Washington, Epidemiol, Seattle, WA 98195 USA.
147Albert Einstein Coll Med, New York, NY USA.
148Wake Forest Baptist Hlth, Biostat Sci, Winston Salem, NC USA.
149Lundquist Inst, Inst Translat Genom & Populat Sci, Torrance, CA USA.
150Univ Colorado, Univ Minnesota, Boulder, CO 80309 USA.
151Brigham & Womens Hosp, Partnersorg, 75 Francis St, Boston, MA 02115 USA.
152Henry Ford Hlth Syst, Detroit, MI USA.
153AbbVie, Chicago, IL USA.
154Astra Zeneca, Cambridge, England.
155Biogen, Cambridge, MA USA.
156Celgene, Summit, NJ USA.
157Genentech Inc, San Francisco, CA USA.
158GlaxoSmithKline, Brentford, England.
159Merck, Kenilworth, NJ USA.
160Pfizer, New York, NY USA.
161Sanofi, Paris, France.
162Univ Helsinki, HiLIFE, Helsinki, Finland.
163Inst Mol Med Finland, HiLIFE, Helsinki, Finland.
164Univ Turku, Auria Biobank, Hosp Dist Southwest, Turku, Finland.
165Natl Inst Hlth & Welf Helsinki, THL Biobank, Helsinki, Finland.
166Finnish Hematol Registry & Clin Biobank, Finnish Red Cross Blood Serv, Helsinki, Finland.
167Hosp Dist Helsinki & Uusimaa, Helsinki, Finland.
168Univ Oulu, Northern Ostrobothnia Hosp Dist, Northern Finland Biobank Borealis, Oulu, Finland.
169Univ Tampere, Finnish Clin Biobank Tampere, Pirkanmaa Hosp Dist, Tampere, Finland.
170Univ Eastern Finland, Biobank Eastern Finland, Northern Savo Hosp Dist, Kuopio, Finland.
171Univ Jyvskyl, Cent Finland Biobank, Cent Finland Hlth Care Dist, Jyvskyl, Finland.
172Business Finland, Helsinki, Finland.
173Northern Savo Hosp Dist, Kuopio, Finland.
174Northern Ostrobothnia Hosp Dist, Oulu, Finland.
175Pirkanmaa Hosp Dist, Tampere, Finland.
176Hosp Dist Southwest Finland, Turku, Finland.
177Natl Inst Hlth & Welf Helsinki, Helsinki, Finland.
178Cent Finland Hlth Care Dist, Jyvskyl, Finland.
179Univ Hosp Dist, Hosp Dist Helsinki & Uusimaa, Finland BB HUS, Helsinki, Finland.
180Auria Biobank, Turku, Finland.
181THL Biobank, Helsinki, Finland.
182Helsinki Biobank, Helsinki, Finland.
183Cent Finland Biobank, Jyvskyl, Finland.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.7 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2022040627379
Language: English
Published: Springer Nature, 2021
Publish Date: 2022-04-06
Description:

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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Series: Nature communications
ISSN: 2041-1723
ISSN-E: 2041-1723
ISSN-L: 2041-1723
Volume: 12
Issue: 1
Article number: 2182
DOI: 10.1038/s41467-021-22339-1
OADOI: https://oadoi.org/10.1038/s41467-021-22339-1
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
3111 Biomedicine
Subjects:
Funding: This work was supported by grants from the National Heart, Lung, and Blood Institute (NHLBI): R01HL142711 (to P.N. and G.M.P.), K08HL140203 supported by a Hassenfeld Scholar Award from the Massachusetts General Hospital, Fondation Leducq (TNE-18CVD04), and additional grants from the National Heart, Lung, and Blood Institute (R01HL148565 and R01HL148050). P.S.de.V. is supported by American Heart Association grant number 18CDA34110116. B.E.C. and J.L. are supported by R35HL135818, HL113338, and HL46380. B.E.C. is also supported by K01HL135405. S.L. is supported by NIH grant 1R01HL139731 and American Heart Association 18SFRN34250007. Whole-genome sequencing (WGS) for the Trans-Omics in Precision Medicine Institute (NHLBI). Centralized read mapping and genotype calling, along with variant quality metrics and filtering were provided by the TOPMed Informatics Research Center (3R01HL-117626-02S1; contract HHSN268201800002I). Phenotype harmonization, data management, sample-identity QC, and general study coordination were provided by the TOPMed Data Coordinating Center (3R01HL-120393-02S1; contract HHSN268201800001I). We gratefully acknowledge the studies and participants who provided biological samples and data for TOPMed. Please refer to Supplementary Notes 1-4 for study-specific acknowledgements. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.
Copyright information: © 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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