15 results on '"Irvin, M. R."'
Search Results
2. APOL1, CDKN2A/CDKN2B, and HDAC9 polymorphisms and small vessel ischemic stroke
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Akinyemi, R., Tiwari, H. K., Arnett, D. K., Ovbiagele, B., Irvin, M. R., Wahab, K., Sarfo, F., Srinivasasainagendra, V., Adeoye, A., Perry, R. T., Akpalu, A., Jenkins, C., Arulogun, O., Gebregziabher, M., Owolabi, L., Obiako, R., Sanya, E., Komolafe, M., Fawale, M., Adebayo, P., Osaigbovo, G., Sunmonu, T., Olowoyo, P., Chukwuonye, I., Obiabo, Y., Onoja, A., Akinyemi, J., Ogbole, G., Melikam, S., Saulson, R., and Owolabi, M.
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- 2018
- Full Text
- View/download PDF
3. The effects of genes implicated in cardiovascular disease on blood pressure response to treatment among treatment-naive hypertensive African Americans in the GenHAT study
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Do, A N, Lynch, A I, Claas, S A, Boerwinkle, E, Davis, B R, Ford, C E, Eckfeldt, J H, Tiwari, H K, Arnett, D K, and Irvin, M R
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- 2016
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4. RYR3 gene polymorphisms and cardiovascular disease outcomes in the context of antihypertensive treatment
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Lynch, A I, Irvin, M R, Boerwinkle, E, Davis, B R, Vaughan, L K, Ford, C E, Aissani, B, Eckfeldt, J H, Arnett, D K, and Shrestha, S
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- 2013
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5. Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
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Natarajan, P. (Pradeep), Pampana, A. (Akhil), Graham, S. E. (Sarah E.), Ruotsalainen, S. E. (Sanni E.), Perry, J. A. (James A.), de Vries, P. S. (Paul S.), Broome, J. G. (Jai G.), Pirruccello, J. P. (James P.), Honigbere, M. C. (Michael C.), Aragam, K. (Krishna), Wolford, B. (Brooke), Brody, J. A. (Jennifer A.), Antonacci-Fulton, L. (Lucinda), Arden, M. (Moscati), Aslibekyan, S. (Stella), Assimes, T. L. (Themistocles L.), Ballantyne, C. M. (Christie M.), Bielak, L. F. (Lawrence F.), Bisl, J. C. (Joshua C.), Cade, B. E. (Brian E.), Do, R. (Ron), Doddapaneni, H. (Harsha), Emery, L. S. (Leslie S.), Hung, Y.-J. (Yi-Jen), Irvin, M. R. (Marguerite R.), Khan, A. T. (Alyna T.), Lange, L. (Leslie), Lee, J. (Jiwon), Lemaitre, R. N. (Rozenn N.), Martin, L. W. (Lisa W.), Metcalf, G. (Ginger), Montasser, M. E. (May E.), Moon, J.-Y. (Jee-Young), Muzny, D. (Donna), Connell, J. R. (Jeffrey R. O.), Palmer, N. D. (Nicholette D.), Peralta, J. M. (Juan M.), Peyser, P. A. (Patricia A.), Stilp, A. M. (Adrienne M.), Tsai, M. (Michael), Wang, F. F. (Fei Fei), Weeks, D. E. (Daniel E.), Yanek, L. R. (Lisa R.), Wilson, J. G. (James G.), Abecasis, G. (Goncalo), Arnett, D. K. (Donna K.), Becker, L. C. (Lewis C.), Blangercy, J. (John), Boerwinkle, E. (Eric), Bowden, D. W. (Donald W.), Chang, Y.-C. (Yi-Cheng), Chen, Y. I. (Yii-Der, I), Choi, W. J. (Won Jung), Correa, A. (Adolfo), Curran, J. E. (Joanne E.), Daly, M. J. (Mark J.), DutcherE, S. K. (Susan K.), Ellinor, P. T. (Patrick T.), Fornage, M. (Myriam), Freedman, B. I. (Barry, I), Gabriel, S. (Stacey), Germer, S. (Soren), Gibbs, R. A. (Richard A.), He, J. (Jiang), Hveem, K. (Kristian), Jarvik, G. P. (Gail P.), Kaplan, R. C. (Robert C.), Kardia, S. L. (Sharon L. R.), Kennyn, E. (Eimear), Kim, R. W. (Ryan W.), Kooperberg, C. (Charles), Laurie, C. C. (Cathy C.), Lee, S. (Seonwook), Lloyd-Jones, D. M. (Don M.), Loos, R. J. (Ruth J. F.), Lubitz, S. A. (Steven A.), Mathias, R. A. (Rasika A.), Martinez, K. A. (Karine A. Viaud), McGarvey, S. T. (Stephen T.), Mitche, B. D. (Braxton D.), Nickerson, D. A. (Deborah A.), North, K. E. (Kari E.), Palotie, A. (Aarno), Park, C. J. (Cheol Joo), Psat, B. M. (Bruce M. Y.), Rao, D. C. (D. C.), Redline, S. (Susan), Reiner, A. P. (Alexander P.), Seo, D. (Daekwan), Seo, J.-S. (Jeong-Sun), Smith, A. V. (Albert, V), Tracy, R. P. (Russell P.), Kathiresan, S. (Sekar), Cupples, L. A. (L. Adrienne), Rotten, J. I. (Jerome, I), Morrison, A. C. (Alanna C.), Rich, S. S. (Stephen S.), Ripatti, S. (Samuli), Wilier, C. (Cristen), Peloso, G. M. (Gina M.), Vasan, R. S. (Ramachandran S.), Abe, N. (Namiko), Albert, C. (Christine), Almasy, L. (Laura), Alonso, A. (Alvaro), Ament, S. (Seth), Anderson, P. (Peter), Applebaum-Bowden, D. (Deborah), Arking, D. (Dan), Ashley-Koch, A. (Allison), Auer, P. (Paul), Avramopoulos, D. (Dimitrios), Barnard, J. (John), Barnes, K. (Kathleen), Barr, R. G. (R. Graham), Barron-Casella, E. (Emily), Beaty, T. (Terri), Becker, D. (Diane), Beer, R. (Rebecca), Begum, F. (Ferdouse), Beitelshees, A. (Amber), Benjamin, E. (Emelia), Bezerra, M. (Marcos), Bielak, L. (Larry), Blackwel, T. (Thomas), Bowler, R. (Russell), Broecke, U. (Ulrich), Bunting, K. (Karen), Burchard, E. (Esteban), Buth, E. (Erin), Cardwel, J. (Jonathan), Carty, C. (Cara), Casaburi, R. (Richard), Casella, J. (James), Chaffin, M. (Mark), Chang, C. (Christy), Chasman, D. (Daniel), Chavan, S. (Sameer), Chen, B.-J. (Bo-Juen), Chen, W.-M. (Wei-Min), Chol, M. (Michael), Choi, S. H. (Seung Hoan), Chuang, L.-M. (Lee-Ming), Chung, M. (Mina), Conomos, M. P. (Matthew P.), Cornell, E. (Elaine), Crapo, J. (James), Curtis, J. (Jeffrey), Custer, B. (Brian), Damcott, C. (Coleen), Darbar, D. (Dawood), Das, S. (Sayantan), David, S. (Sean), Davis, C. (Colleen), Daya, M. (Michelle), de Andrade, M. (Mariza), DeBaunuo, M. (Michael), Duan, Q. (Qing), Devine, R. D. (Ranjan Deka Dawn DeMeo Scott), Duggirala, Q. R. (Qing Ravi), Durda, J. P. (Jon Peter), Dutcher, S. (Susan), Eaton, C. (Charles), Ekunwe, L. (Lynette), Farber, C. (Charles), Farnaml, L. (Leanna), Fingerlin, T. (Tasha), Flickinger, M. (Matthew), Franceschini, N. (Nora), Fu, M. (Mao), Fullerton, S. M. (Stephanie M.), Fulton, L. (Lucinda), Gan, W. (Weiniu), Gao, Y. (Yan), Gass, M. (Margery), Ge, B. (Bruce), Geng, X. P. (Xiaoqi Priscilla), Gignoux, C. (Chris), Gladwin, M. (Mark), Glahn, D. (David), Gogarten, S. (Stephanie), Gong, D.-W. (Da-Wei), Goring, H. (Harald), Gu, C. C. (C. Charles), Guan, Y. (Yue), Guo, X. (Xiuqing), Haessler, J. (Jeff), Hall, M. (Michael), Harris, D. (Daniel), Hawle, N. Y. (Nicola Y.), Heavner, B. (Ben), Heckbert, S. (Susan), Hernandez, R. (Ryan), Herrington, D. (David), Hersh, C. (Craig), Hidalgo, B. (Bertha), Hixson, J. (James), Hokanson, J. (John), Hong, E. (Elliott), Hoth, K. (Karin), Hsiung, C. A. (Chao Agnes), Huston, H. (Haley), Hwu, C. M. (Chii Min), Jackson, R. (Rebecca), Jain, D. (Deepti), Jaquish, C. (Cashell), Jhun, M. A. (Min A.), Johnsen, J. (Jill), Johnson, A. (Andrew), Johnson, C. (Craig), Johnston, R. (Rich), Jones, K. (Kimberly), Kang, H. M. (Hyun Min), Kaufman, L. (Laura), Kell, S. Y. (Shannon Y.), Kessler, M. (Michael), Kinney, G. (Greg), Konkle, B. (Barbara), Kramer, H. (Holly), Krauter, S. (Stephanie), Lange, C. (Christoph), Lange, E. (Ethan), Laurie, C. (Cecelia), LeBoff, M. (Meryl), Lee, S. S. (Seunggeun Shawn), Lee, W.-J. (Wen-Jane), LeFaive, J. (Jonathon), Levine, D. (David), Levy, D. (Dan), Lewis, J. (Joshua), Li, Y. (Yun), Lin, H. (Honghuang), Lin, K. H. (Keng Han), Lin, X. (Xihong), Liu, S. (Simin), Liu, Y. (Yongmei), Lunetta, K. (Kathryn), Luo, J. (James), Mahaney, M. (Michael), Make, B. (Barry), Manichaikul, A. (Ani), Mansonl, J. (JoAnn), Margolin, L. (Lauren), Mathai, S. (Susan), McArdle, P. (Patrick), Mcdonald, M.-L. (Merry-Lynn), McFarland, S. (Sean), McHugh, C. (Caitlin), Mei, H. (Hao), Meyers, D. A. (Deborah A.), Mikulla, J. (Julie), Min, N. (Nancy), Minear, M. (Mollie), Minster, R. L. (Ryan L.), Musani, S. (Solomon), Mwasongwe, S. (Stanford), Mychaleckyj, J. C. (Josyf C.), Nadkarni, G. (Girish), Naik, R. (Rakhi), Naseri, T. (Take), Nekhai, S. (Sergei), Nelson, S. C. (Sarah C.), Nickerson, D. (Deborah), Connell, J. O. (Jeff O.), Connor, T. O. (Tim O.), Ochs-Balcom, H. (Heather), Pankow, J. (James), Papanicolaou, G. (George), Parkerl, M. (Margaret), Parsa, A. (Afshin), Penchey, S. (Sara), Perez, M. (Marco), Peters, U. (Ulrike), Phillips, L. S. (Lawrence S.), Phillips, S. (Sam), Pollin, T. (Toni), Post, W. (Wendy), Becker, J. P. (Julia Powers), Boorgula, M. P. (Meher Preethi), Preuss, M. (Michael), Prokopenko, D. (Dmitry), Qasba, P. (Pankaj), Qiao, D. (Dandi), Rafaels, N. (Nicholas), Raffield, L. (Laura), Rasmussen-Torvik, L. (Laura), Ratan, A. (Aakrosh), Reed, R. (Robert), Reganl, E. (Elizabeth), Reupena, M. S. (Muagututi Sefuiva), Rice, K. (Ken), Roden, D. (Dan), Roselli, C. (Carolina), Ruczinski, I. (Ingo), Russel, P. (Pamela), Ruuska, S. (Sarah), Ryan, K. (Kathleen), Sabino, E. C. (Ester Cerdeira), Sakornsakolpatl, P. (Phuwanat), Salzberg, S. (Steven), Sandow, K. (Kevin), Sankaran, V. G. (Vijay G.), Scheller, C. (Christopher), Schmidt, E. (Ellen), Schwander, K. (Karen), Schwartz, D. (David), Sciurba, F. (Frank), Seidman, C. (Christine), Seidman, J. (Jonathan), Sheehan, V. (Vivien), Shetty, A. (Amol), Shetty, A. (Aniket), Sheu, W. H. (Wayne Hui-Heng), Shoemaker, M. B. (M. Benjamin), Silver, B. (Brian), Silvermanl, E. (Edwin), Smith, J. (Jennifer), Smith, J. (Josh), Smith, N. (Nicholas), Smith, T. (Tanja), Smoller, S. (Sylvia), Snively, B. (Beverly), Soferlm, T. (Tamar), Streeten, E. (Elizabeth), Su, J. L. (Jessica Lasky), Sung, Y. J. (Yun Ju), Sylvia, J. (Jody), Sztalryd, C. (Carole), Taliun, D. (Daniel), Tang, H. (Hua), Taub, M. (Margaret), Taylor, K. D. (Kent D.), Taylor, S. (Simeon), Telen, M. (Marilyn), Thornton, T. A. (Timothy A.), Tinker, L. (Lesley), Tirschwel, D. (David), Tiwari, H. (Hemant), Vaidya, D. (Dhananjay), VandeHaar, P. (Peter), Vrieze, S. (Scott), Walker, T. (Tarik), Wallace, R. (Robert), Waits, A. (Avram), Wan, E. (Emily), Wang, H. (Heming), Watson, K. (Karol), Weir, B. (Bruce), Weiss, S. (Scott), Weng, L.-C. (Lu-Chen), Williams, K. (Kayleen), Williams, L. K. (L. Keoki), Wilson, C. (Carla), Wong, Q. (Quenna), Xu, H. (Huichun), Yang, I. (Ivana), Yang, R. (Rongze), Zaghlou, N. (Norann), Zekavat, M. (Maryam), Zhang, Y. (Yingze), Zhao, S. X. (Snow Xueyan), Zhao, W. (Wei), Zni, D. (Degui), Zhou, X. (Xiang), Zhu, X. (Xiaofeng), Zody, M. (Michael), Zoellner, S. (Sebastian), Daly, M. (Mark), Jacob, H. (Howard), Matakidou, A. (Athena), Runz, H. (Heiko), John, S. (Sally), Plenge, R. (Robert), McCarthy, M. (Mark), Hunkapiller, J. (Julie), Ehm, M. (Meg), Waterworth, D. (Dawn), Fox, C. (Caroline), Malarstig, A. (Anders), Klinger, K. (Kathy), Call, K. (Kathy), Mkel, T. (Tomi), Kaprio, J. (Jaakko), Virolainen, P. (Petri), Pulkki, K. (Kari), Kilpi, T. (Terhi), Perola, M. (Markus), Partanen, J. (Jukka), Pitkranta, A. (Anne), Kaarteenaho, R. (Riitta), Vainio, S. (Seppo), Savinainen, K. (Kimmo), Kosma, V.-M. (Veli-Matti), Kujala, U. (Urho), Tuovila, O. (Outi), Hendolin, M. (Minna), Pakkanen, R. (Raimo), Waring, J. (Jeff), Riley-Gillis, B. (Bridget), Liu, J. (Jimmy), Biswas, S. (Shameek), Diogo, D. (Dorothee), Marshall, C. (Catherine), Hu, X. (Xinli), Gossel, M. (Matthias), Schleutker, J. (Johanna), Arvas, M. (Mikko), Hinttala, R. (Reetta), Kettunen, J. (Johannes), Laaksonen, R. (Reijo), Mannermaa, A. (Arto), Paloneva, J. (Juha), Soininen, H. (Hilkka), Julkunen, V. (Valtteri), Remes, A. (Anne), Klviinen, R. (Reetta), Hiltunen, M. (Mikko), Peltola, J. (Jukka), Tienari, P. (Pentti), Rinne, J. (Juha), Ziemann, A. (Adam), Waring, J. (Jeffrey), Esmaeeli, S. (Sahar), Smaoui, N. (Nizar), Lehtonen, A. (Anne), Eaton, S. (Susan), Landenper, S. (Sanni), Michon, J. (John), Kerchner, G. (Geoff), Bowers, N. (Natalie), Teng, E. (Edmond), Eicher, J. (John), Mehta, V. (Vinay), Gormle, P. Y. (Padhraig Y.), Linden, K. (Kari), Whelan, C. (Christopher), Xu, F. (Fanli), Pulford, D. (David), Frkkil, M. (Martti), Pikkarainen, S. (Sampsa), Jussila, A. (Airi), Blomster, T. (Timo), Kiviniemi, M. (Mikko), Voutilainen, M. (Markku), Georgantas, B. (Bob), Heap, G. (Graham), Rahimov, F. (Fedik), Usiskin, K. (Keith), Maranville, J. (Joseph), Lu, T. (Tim), Oh, D. (Danny), Kalpala, K. (Kirsi), Miller, M. (Melissa), McCarthy, L. (Linda), Eklund, K. (Kari), Palomki, A. (Antti), Isomki, P. (Pia), Piri, L. (Laura), Kaipiainen-Seppnen, O. (Oili), Lertratanaku, A. (Apinya), Bing, D. C. (David Close Marla Hochfeld Nan), Gordillo, J. E. (Jorge Esparza), Mars, N. (Nina), Laitinen, T. (Tarja), Pelkonen, M. (Margit), Kauppi, P. (Paula), Kankaanranta, H. (Hannu), Harju, T. (Terttu), Greenberg, S. (Steven), Chen, H. (Hubert), Betts, J. (Jo), Ghosh, S. (Soumitra), Salomaa, V. (Veikko), Niiranen, T. (Teemu), Juonala, M. (Markus), Metsrinne, K. (Kaj), Khnen, M. (Mika), Junttila, J. (Juhani), Laakso, M. (Markku), Pihlajamki, J. (Jussi), Sinisalo, J. (Juha), Taskinen, M.-R. (Marja-Riitta), Tuomi, T. (Tiinamaija), Laukkanen, J. (Jari), Challis, B. (Ben), Peterson, A. (Andrew), Chu, A. (Audrey), Parkkinen, J. (Jaakko), Muslin, A. (Anthony), Joensuu, H. (Heikki), Meretoja, T. (Tuomo), Aaltonen, L. (Lauri), Auranen, A. (Annika), Karihtala, P. (Peeter), Kauppila, S. (Saila), Auvinen, P. (Pivi), Elenius, K. (Klaus), Popovic, R. (Relja), Schutzman, J. (Jennifer), Loboda, A. (Andrey), Chhibber, A. (Aparna), Lehtonen, H. (Heli), McDonough, S. (Stefan), Crohns, M. (Marika), Kulkarni, D. (Diptee), Kaarniranta, K. (Kai), Turunen, J. (Joni), Ollila, T. (Terhi), Seitsonen, S. (Sanna), Uusitalo, H. (Hannu), Aaltonen, V. (Vesa), Uusitalo-Jrvinen, H. (Hannele), Luodonp, M. (Marja), Hautala, N. (Nina), Strauss, E. (Erich), Chen, H. (Hao), Podgornaia, A. (Anna), Hoffman, J. (Joshua), Tasanen, K. (Kaisa), Huilaja, L. (Laura), Hannula-Jouppi, K. (Katariina), Salmi, T. (Teea), Peltonen, S. (Sirkku), Koulu, L. (Leena), Harvima, I. (Ilkka), Wu, Y. (Ying), Choy, D. (David), Jalanko, A. (Anu), Kajanne, R. (Risto), Lyhs, U. (Ulrike), Kaunisto, M. (Mari), Davis, J. W. (Justin Wade), Quarless, D. (Danjuma), Petrovski, S. (Slav), Chen, C.-Y. (Chia-Yen), Bronson, P. (Paola), Yang, R. (Robert), Chang, D. (Diana), Bhangale, T. (Tushar), Holzinger, E. (Emily), Wang, X. (Xulong), Chen, X. (Xing), Auro, K. (Kirsi), Wang, C. (Clarence), Xu, E. (Ethan), Auge, F. (Franck), Chatelain, C. (Clement), Kurki, M. (Mitja), Karjalainen, J. (Juha), Havulinna, A. (Aki), Palin, K. (Kimmo), Palta, P. (Priit), Parolo, P. D. (Pietro Della Briotta), Zhou, W. (Wei), Lemmel, S. (Susanna), Rivas, M. (Manuel), Harju, J. (Jarmo), Lehisto, A. (Arto), Ganna, A. (Andrea), Llorens, V. (Vincent), Karlsson, A. (Antti), Kristiansson, K. (Kati), Hyvrinen, K. (Kati), Ritari, J. (Jarmo), Wahlfors, T. (Tiina), Koskinen, M. (Miika), Pylkäs, K. (Katri), Kalaoja, M. (Marita), Karjalainen, M. (Minna), Mantere, T. (Tuomo), Kangasniemi, E. (Eeva), Heikkinen, S. (Sami), Laakkonen, E. (Eija), Kononen, J. (Juha), Loukola, A. (Anu), Laiho, P. (Pivi), Sistonen, T. (Tuuli), Kaiharju, E. (Essi), Laukkanen, M. (Markku), Jrvensivu, E. (Elina), Lhteenmki, S. (Sini), Mnnikk, L. (Lotta), Wong, R. (Regis), Mattsson, H. (Hannele), Hiekkalinna, T. (Tero), Jimnez, M. G. (Manuel Gonzlez), Donner, K. (Kati), Prn, K. (KaIle), Nunez-Fontarnau, J. (Javier), Kilpelinen, E. (Elina), Sipi, T. P. (Timo P.), Brein, G. (Georg), Dada, A. (Alexander), Awaisa, G. (Ghazal), Shcherban, A. (Anastasia), Sipil, T. (Tuomas), Laivuori, H. (Hannele), Kiiskinen, T. (Tuomo), Siirtola, H. (Harri), Tabuenca, J. G. (Javier Gracia), Kallio, L. (Lila), Soini, S. (Sirpa), Pitknen, K. (Kimmo), and Kuopio, T. (Teijo)
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Cardiovascular genetics ,Genome-wide association studies - 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.
- Published
- 2021
6. A DNA methylation biomarker of alcohol consumption
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Liu, C, Marioni, R E, Hedman, Åsa K, Pfeiffer, L, Tsai, P-C, Reynolds, L M, Just, A C, Duan, Q, Boer, C G, Tanaka, T, Elks, C E, Aslibekyan, S, Brody, J A, Kühnel, B, Herder, C, Almli, L M, Zhi, D, Wang, Y, Huan, T, Yao, C, Mendelson, M M, Joehanes, R, Liang, L, Love, S-A, Guan, W, Shah, S, McRae, A F, Kretschmer, A, Prokisch, H, Strauch, K, Peters, A, Visscher, P M, Wray, N R, Guo, X, Wiggins, K L, Smith, A K, Binder, E B, Ressler, K J, Irvin, M R, Absher, D M, Hernandez, D, Ferrucci, L, Bandinelli, S, Lohman, K, Ding, J, Trevisi, L, Gustafsson, Stefan, Sandling, Johanna K., Stolk, L, Uitterlinden, A G, Yet, I, Castillo-Fernandez, J E, Spector, T D, Schwartz, J D, Vokonas, P, Lind, Lars, Li, Y, Fornage, M, Arnett, D K, Wareham, N J, Sotoodehnia, N, Ong, K K, van Meurs, J B J, Conneely, K N, Baccarelli, A A, Deary, I J, Bell, J T, North, K E, Liu, Y, Waldenberger, M, London, S J, Ingelsson, Erik, Levy, D, Wareham, Nicholas [0000-0003-1422-2993], Ong, Kenneth [0000-0003-4689-7530], Apollo - University of Cambridge Repository, Erasmus MC other, Internal Medicine, and Epidemiology
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Adult ,Male ,Alcohol Drinking ,Ethanol ,Black People ,DNA Methylation ,Middle Aged ,White People ,Epigenesis, Genetic ,Annan medicinsk grundvetenskap ,Genetics ,Humans ,CpG Islands ,Female ,Other Basic Medicine ,Alcohol-Related Disorders ,Biomarkers ,Aged ,Genome-Wide Association Study - Abstract
The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted PDe tio första författarna delar på förstaförfattarskapet. De sex sista författarna delar på sistaförfattarskapet.
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- 2018
- Full Text
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7. The power of genetic diversity in genome-wide association studies of lipids
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Graham, Sarah E, Clarke, Shoa L, Wu, Kuan-Han H, Kanoni, Stavroula, Zajac, Greg JM, Ramdas, Shweta, Surakka, Ida, Ntalla, Ioanna, Vedantam, Sailaja, Winkler, Thomas W, Locke, Adam E, Marouli, Eirini, Hwang, Mi Yeong, Han, Sohee, Narita, Akira, Choudhury, Ananyo, Bentley, Amy R, Ekoru, Kenneth, Verma, Anurag, Trivedi, Bhavi, Martin, Hilary C, Hunt, Karen A, Hui, Qin, Klarin, Derek, Zhu, Xiang, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F, Holm, Hilma, Olafsson, Isleifur, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M, Rasheed, Humaira, Ruotsalainen, Sanni E, Havulinna, Aki S, Veturi, Yogasudha, Feng, QiPing, Rosenthal, Elisabeth A, Lingren, Todd, Pacheco, Jennifer Allen, Pendergrass, Sarah A, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E, Campbell, Archie, Lin, Kuang, Millwood, Iona Y, Hindy, George, Rasheed, Asif, Faul, Jessica D, Zhao, Wei, Weir, David R, Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Mahajan, Anubha, Brown, Michael R, Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M, Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian’an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Willemsen, Gonneke, Wood, Andrew R, Ji, Yingji, Gao, Zishan, Haworth, Simon, Mitchell, Ruth E, Chai, Jin Fang, Aadahl, Mette, Yao, Jie, Manichaikul, Ani, Warren, Helen R, Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L, Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Sidore, Carlo, Fiorillo, Edoardo, McDaid, Aaron F, Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T, Thuesen, Betina H, Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Lamina, Claudia, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Daw, E Warwick, Zmuda, Joseph M, Mitchell, Jonathan S, Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A, Feitosa, Mary F, Wojczynski, Mary K, Preuss, Michael, Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W, Engmann, Jorgen, Kember, Rachel L, Slieker, Roderick C, Lo, Ken Sin, Zilhao, Nuno R, Le, Phuong, Kleber, Marcus E, Delgado, Graciela E, Huo, Shaofeng, Ikeda, Daisuke D, Iha, Hiroyuki, Yang, Jian, Liu, Jun, Leonard, Hampton L, Marten, Jonathan, Schmidt, Börge, Arendt, Marina, Smyth, Laura J, Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Ahmed, Meraj, Jackson, Anne U, Irvin, Marguerite R, Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul RHJ, Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A, Chai, Xiaoran, Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N, Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C, Wang, Ya Xing, Wei, Wen B., Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Hung, Yi-Jen, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A, Gorski, Mathias, Brumat, Marco, Meidtner, Karina, Bielak, Lawrence F, Smith, Jennifer A, Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Xue, Chao, Zhang, Jifeng, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J, Pitkänen, Niina, Cade, Brian E, Lee, Jiwon, van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Zimmermann, Martina E, Lee, Jong Young, Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W, Wang, Carol A, Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hildalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O, van Setten, Jessica, Li, Xiaoyin, Schwander, Karen, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D, Reiner, Alexander P, Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Highland, Heather M, Young, Kristin L, Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C, Nadkarni, Girish N., Launer, Lenore J, Li, Huaixing, Nalls, Mike A, Raitakari, Olli T, Ichihara, Sahoko, Wild, Sarah H, Nelson, Christopher P, Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S, Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, Bhatti, Konain Fatima, de Kleijn, Dominique, de Borst, Gert J., Kim, Eung Kweon, Adams, Hieab H.H., Ikram, M. Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W, Kraaijeveld, Adriaan O, Beulens, Joline WJ, Shu, Xiao-Ou, Rallidis, Loukianos S, Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W, Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Chen, Yii-Der Ida, Pennell, Craig E, Mori, Trevor A, Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M, Stark, Klaus J, Völzke, Henry, Homuth, Georg, Evans, Michele K, Zonderman, Alan B, Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E, Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J, Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Chen, Y Eugene, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Kardia, Sharon LR, Kato, Norihiro, Schulze, Matthias B, Girotto, Giorgia, Jung, Bettina, Böger, Carsten A, Joshi, Peter K, Bennett, David A, De Jager, Philip L, Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J, Munroe, Patricia B, Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B., Samani, Nilesh J, Chasman, Daniel I., Kaprio, Jaakko, Pajukanta, Päivi, Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A, Adair, Linda S, Bechayda, Sonny Augustin, de Silva, H. Janaka, Wickremasinghe, Ananda R, Krauss, Ronald M, Wu, Jer-Yuarn, Zheng, Wei, den Hollander, Anneke I, Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G, Lind, Lars, Heng, Chew-Kiat, Nelson, Amanda E, Golightly, Yvonne M, Wilson, James F, Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J, Rao, D C, Arnett, Donna K, Walker, Mark, Koistinen, Heikki A, Chandak, Giriraj R, Yajnik, Chittaranjan S, Mercader, Josep M, Tusie-Luna, Teresa, Aguilar-Salinas, Carlos, Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, E Shyong, van Dam, Rob M, Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F, McKnight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, McCarthy, Mark I, Palmer, Colin NA, Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M, Lu, Fan, Qu, Jia, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Parra, Esteban J, Cruz, Miguel, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, Hart, Leen M t, Elders, Petra JM, Rader, Daniel J, Damrauer, Scott M, Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D, Loos, Ruth J.F., Province, Michael A, Psaty, Bruce M, Brandslund, Ivan, Pramstaller, Peter P, Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F.A., Kiemeney, Lambertus ALM, de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W, Linneberg, Allan, Jukema, J. Wouter, Khera, Amit V, Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Cucca, Francesco, Mook-Kanamori, Dennis O, van Dijk, Ko Willems, Watkins, Hugh, Strachan, David P, Grarup, Niels, Sever, Peter, Poulter, Neil, Rotter, Jerome I, Dantoft, Thomas M, Karpe, Fredrik, Neville, Matt J, Timpson, Nicholas J, Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T, Pedersen, Nancy L, Magnusson, Patrik KE, Boomsma, Dorret I, de Geus, Eco JC, Cupples, L Adrienne, van Meurs, Joyce B.J., Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J, Langenberg, Claudia, Zeggini, Eleftheria, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C, Kooner, Jaspal S, de Vries, Paul S, Morrison, Alanna C, North, Kari E., Daviglus, Martha, Kraft, Peter, Martin, Nicholas G, Whitfield, John B, Abbas, Shahid, Saleheen, Danish, Walters, Robin G, Holmes, Michael V, Black, Corri, Smith, Blair H, Justice, Anne E, Baras, Aris, Buring, Julie E, Ridker, Paul M, Chasman, Daniel I, Kooperberg, Charles, Wei, Wei-Qi, Jarvik, Gail P, Namjou, Bahram, Hayes, M. Geoffrey, Ritchie, Marylyn D, Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Thorsteinsdottir, Unnur, Stefansson, Kari, Ho, Yuk-Lam, Lynch, Julie A, Rader, Daniel, Tsao, Phil S, Chang, Kyong-Mi, Cho, Kelly, O’Donnell, Christopher J, Gaziano, John M, Wilson, Peter, Rotimi, Charles N, Hazelhurst, Scott, Ramsay, Michèle, Trembath, Richard C, van Heel, David A, Tamiya, Gen, Yamamoto, Masayuki, Kim, Bong-Jo, Mohlke, Karen L, Frayling, Timothy M, Hirschhorn, Joel N, Kathiresan, Sekar, Boehnke, Michael, Natarajan, Pradeep, Peloso, Gina M, Brown, Christopher D, Morris, Andrew P, Assimes, Themistocles L, Deloukas, Panos, Sun, Yan V, Willer, Cristen J, VA Million Veteran Program, Global Lipids Genetics Consortium, Internal Medicine, Epidemiology, Radiology & Nuclear Medicine, Graham, S. E., Clarke, S. L., Wu, K. -H. H., Kanoni, S., Zajac, G. J. M., Ramdas, S., Surakka, I., Ntalla, I., Vedantam, S., Winkler, T. W., Locke, A. E., Marouli, E., Hwang, M. Y., Han, S., Narita, A., Choudhury, A., Bentley, A. R., Ekoru, K., Verma, A., Trivedi, B., Martin, H. C., Hunt, K. A., Hui, Q., Klarin, D., Zhu, X., Thorleifsson, G., Helgadottir, A., Gudbjartsson, D. F., Holm, H., Olafsson, I., Akiyama, M., Sakaue, S., Terao, C., Kanai, M., Zhou, W., Brumpton, B. M., Rasheed, H., Ruotsalainen, S. E., Havulinna, A. S., Veturi, Y., Feng, Q. P., Rosenthal, E. A., Lingren, T., Pacheco, J. A., Pendergrass, S. A., Haessler, J., Giulianini, F., Bradford, Y., Miller, J. E., Campbell, A., Lin, K., Millwood, I. Y., Hindy, G., Rasheed, A., Faul, J. D., Zhao, W., Weir, D. R., Turman, C., Huang, H., Graff, M., Mahajan, A., Brown, M. R., Zhang, W., Yu, K., Schmidt, E. M., Pandit, A., Gustafsson, S., Yin, X., Luan, J., Zhao, J. -H., Matsuda, F., Jang, H. -M., Yoon, K., Medina-Gomez, C., Pitsillides, A., Hottenga, J. J., Willemsen, G., Wood, A. R., Ji, Y., Gao, Z., Haworth, S., Mitchell, R. E., Chai, J. F., Aadahl, M., Yao, J., Manichaikul, A., Warren, H. R., Ramirez, J., Bork-Jensen, J., Karhus, L. L., Goel, A., Sabater-Lleal, M., Noordam, R., Sidore, C., Fiorillo, E., Mcdaid, A. F., Marques-Vidal, P., Wielscher, M., Trompet, S., Sattar, N., Mollehave, L. T., Thuesen, B. H., Munz, M., Zeng, L., Huang, J., Yang, B., Poveda, A., Kurbasic, A., Lamina, C., Forer, L., Scholz, M., Galesloot, T. E., Bradfield, J. P., Daw, E. W., Zmuda, J. M., Mitchell, J. S., Fuchsberger, C., Christensen, H., Brody, J. A., Feitosa, M. F., Wojczynski, M. K., Preuss, M., Mangino, M., Christofidou, P., Verweij, N., Benjamins, J. W., Engmann, J., Kember, R. L., Slieker, R. C., Lo, K. S., Zilhao, N. R., Le, P., Kleber, M. E., Delgado, G. E., Huo, S., Ikeda, D. D., Iha, H., Yang, J., Liu, J., Leonard, H. L., Marten, J., Schmidt, B., Arendt, M., Smyth, L. J., Canadas-Garre, M., Wang, C., Nakatochi, M., Wong, A., Hutri-Kahonen, N., Sim, X., Xia, R., Huerta-Chagoya, A., Fernandez-Lopez, J. C., Lyssenko, V., Ahmed, M., Jackson, A. U., Irvin, M. R., Oldmeadow, C., Kim, H. -N., Ryu, S., Timmers, P. R. H. J., Arbeeva, L., Dorajoo, R., Lange, L. A., Chai, X., Prasad, G., Lores-Motta, L., Pauper, M., Long, J., Li, X., Theusch, E., Takeuchi, F., Spracklen, C. N., Loukola, A., Bollepalli, S., Warner, S. C., Wang, Y. X., Wei, W. B., Nutile, T., Ruggiero, D., Sung, Y. J., Hung, Y. -J., Chen, S., Liu, F., Kentistou, K. A., Gorski, M., Brumat, M., Meidtner, K., Bielak, L. F., Smith, J. A., Hebbar, P., Farmaki, A. -E., Hofer, E., Lin, M., Xue, C., Zhang, J., Concas, M. P., Vaccargiu, S., van der Most, P. J., Pitkanen, N., Cade, B. E., Lee, J., van der Laan, S. W., Chitrala, K. N., Weiss, S., Zimmermann, M. E., Lee, J. Y., Choi, H. S., Nethander, M., Freitag-Wolf, S., Southam, L., Rayner, N. W., Wang, C. A., Lin, S. -Y., Wang, J. -S., Couture, C., Lyytikainen, L. -P., Nikus, K., Cuellar-Partida, G., Vestergaard, H., Hildalgo, B., Giannakopoulou, O., Cai, Q., Obura, M. O., van Setten, J., Schwander, K., Terzikhan, N., Shin, J. H., Jackson, R. D., Reiner, A. P., Martin, L. W., Chen, Z., Li, L., Highland, H. M., Young, K. L., Kawaguchi, T., Thiery, J., Bis, J. C., Nadkarni, G. N., Launer, L. J., Li, H., Nalls, M. A., Raitakari, O. T., Ichihara, S., Wild, S. H., Nelson, C. P., Campbell, H., Jager, S., Nabika, T., Al-Mulla, F., Niinikoski, H., Braund, P. S., Kolcic, I., Kovacs, P., Giardoglou, T., Katsuya, T., Bhatti, K. F., de Kleijn, D., de Borst, G. J., Kim, E. K., Adams, H. H. H., Ikram, M. A., Asselbergs, F. W., Kraaijeveld, A. O., Beulens, J. W. J., Shu, X. -O., Rallidis, L. S., Pedersen, O., Hansen, T., Mitchell, P., Hewitt, A. W., Kahonen, M., Perusse, L., Bouchard, C., Tonjes, A., Chen, Y. -D. I., Pennell, C. E., Mori, T. A., Lieb, W., Franke, A., Ohlsson, C., Mellstrom, D., Cho, Y. S., Lee, H., Yuan, J. -M., Koh, W. -P., Rhee, S. Y., Woo, J. -T., Heid, I. M., Stark, K. J., Volzke, H., Homuth, G., Evans, M. K., Zonderman, A. B., Polasek, O., Pasterkamp, G., Hoefer, I. E., Redline, S., Pahkala, K., Oldehinkel, A. J., Snieder, H., Biino, G., Schmidt, R., Schmidt, H., Chen, Y. E., Bandinelli, S., Dedoussis, G., Thanaraj, T. A., Kardia, S. L. R., Kato, N., Schulze, M. B., Girotto, G., Jung, B., Boger, C. A., Joshi, P. K., Bennett, D. A., De Jager, P. L., Lu, X., Mamakou, V., Brown, M., Caulfield, M. J., Munroe, P. B., Guo, X., Ciullo, M., Jonas, J. B., Samani, N. J., Kaprio, J., Pajukanta, P., Adair, L. S., Bechayda, S. A., de Silva, H. J., Wickremasinghe, A. R., Krauss, R. M., Wu, J. -Y., Zheng, W., den Hollander, A. I., Bharadwaj, D., Correa, A., Wilson, J. G., Lind, L., Heng, C. -K., Nelson, A. E., Golightly, Y. M., Wilson, J. F., Penninx, B., Kim, H. -L., Attia, J., Scott, R. J., Rao, D. C., Arnett, D. K., Walker, M., Koistinen, H. A., Chandak, G. R., Yajnik, C. S., Mercader, J. M., Tusie-Luna, T., Aguilar-Salinas, C. A., Villalpando, C. G., Orozco, L., Fornage, M., Tai, E. S., van Dam, R. M., Lehtimaki, T., Chaturvedi, N., Yokota, M., Reilly, D. F., Mcknight, A. J., Kee, F., Jockel, K. -H., Mccarthy, M. I., Palmer, C. N. A., Vitart, V., Hayward, C., Simonsick, E., van Duijn, C. M., Lu, F., Qu, J., Hishigaki, H., Lin, X., Marz, W., Parra, E. J., Cruz, M., Gudnason, V., Tardif, J. -C., Lettre, G., 't Hart, L. M., Elders, P. J. M., Damrauer, S. M., Kumari, M., Kivimaki, M., van der Harst, P., Spector, T. D., Loos, R. J. F., Province, M. A., Psaty, B. M., Brandslund, I., Pramstaller, P. P., Christensen, K., Ripatti, S., Widen, E., Hakonarson, H., Grant, S. F. A., Kiemeney, L. A. L. M., de Graaf, J., Loeffler, M., Kronenberg, F., Gu, D., Erdmann, J., Schunkert, H., Franks, P. W., Linneberg, A., Jukema, J. W., Khera, A. V., Mannikko, M., Jarvelin, M. -R., Kutalik, Z., Cucca, F., Mook-Kanamori, D. O., van Dijk, K. W., Watkins, H., Strachan, D. P., Grarup, N., Sever, P., Poulter, N., Rotter, J. I., Dantoft, T. M., Karpe, F., Neville, M. J., Timpson, N. J., Cheng, C. -Y., Wong, T. -Y., Khor, C. C., Sabanayagam, C., Peters, A., Gieger, C., Hattersley, A. T., Pedersen, N. L., Magnusson, P. K. E., Boomsma, D. I., de Geus, E. J. C., Cupples, L. A., van Meurs, J. B. J., Ghanbari, M., Gordon-Larsen, P., Huang, W., Kim, Y. J., Tabara, Y., Wareham, N. J., Langenberg, C., Zeggini, E., Kuusisto, J., Laakso, M., Ingelsson, E., Abecasis, G., Chambers, J. C., Kooner, J. S., de Vries, P. S., Morrison, A. C., North, K. E., Daviglus, M., Kraft, P., Martin, N. G., Whitfield, J. B., Abbas, S., Saleheen, D., Walters, R. G., Holmes, M. V., Black, C., Smith, B. H., Justice, A. E., Baras, A., Buring, J. E., Ridker, P. M., Chasman, D. I., Kooperberg, C., Wei, W. -Q., Jarvik, G. P., Namjou, B., Hayes, M. G., Ritchie, M. D., Jousilahti, P., Salomaa, V., Hveem, K., Asvold, B. O., Kubo, M., Kamatani, Y., Okada, Y., Murakami, Y., Thorsteinsdottir, U., Stefansson, K., Ho, Y. -L., Lynch, J. A., Rader, D. J., Tsao, P. S., Chang, K. -M., Cho, K., O'Donnell, C. J., Gaziano, J. M., Wilson, P., Rotimi, C. N., Hazelhurst, S., Ramsay, M., Trembath, R. C., van Heel, D. A., Tamiya, G., Yamamoto, M., Kim, B. -J., Mohlke, K. L., Frayling, T. M., Hirschhorn, J. N., Kathiresan, S., Boehnke, M., Natarajan, P., Peloso, G. M., Brown, C. D., Morris, A. P., Assimes, T. L., Deloukas, P., Sun, Y. V., Willer, C. J., Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, APH - Methodology, AMS - Ageing & Vitality, and AMS - Sports
- Subjects
blood lipid level ,Multifactorial Inheritance ,GWAS ,blood lipid levels ,cardiovascular disease ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Medizin ,LOCI ,ANCESTRY ,VARIANTS ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] ,Article ,Population Groups ,SDG 3 - Good Health and Well-being ,Humans ,Genetic Predisposition to Disease ,METAANALYSIS ,POLYMORPHISMS ,RISK ,Multidisciplinary ,Cardiovascular Diseases ,Genome-Wide Association Study ,Cardiovascular Diseases/genetics ,Genetic Predisposition to Disease/genetics ,Genome-Wide Association Study/methods ,Polymorphism, Single Nucleotide/genetics ,CHOLESTEROL ,Human Genetics ,INDIVIDUALS ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,DISCOVERY ,LOW-FREQUENCY ,Delivery of Health Care - Abstract
Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use 1 . Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels 2 , heart disease remains the leading cause of death worldwide 3 . Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS 4-23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns 24 . Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine 25 , we anticipate that increased diversity of participants will lead to more accurate and equitable 26 application of polygenic scores in clinical practice.
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- 2021
8. Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
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Yongmei Liu, Tuomas O. Kilpeläinen, Kenneth Rice, Ching-Ti Liu, Jin-Fang Chai, Donna K. Arnett, Dhananjay Vaidya, Nicholette D. Palmer, Lili Milani, Yuri Milaneschi, Leo-Pekka Lyytikäinen, Colleen M. Sitlani, Richard S. Cooper, Gudny Eiriksdottir, Daniel Levy, Jerome I. Rotter, Lihua Wang, Sven Bergmann, Yih Chung Tham, Thomas Meitinger, Lynne E. Wagenknecht, Virginia Fisher, Babatunde L. Salako, Vilmundur Gudnason, Bamidele O. Tayo, Caizheng Yu, Barry I. Freedman, Muhammad Riaz, Kaare Christensen, Ulrich Broeckel, W. James Gauderman, Massimiliano Cocca, Eric Boerwinkle, Meian He, Rob M. van Dam, M. Arfan Ikram, Lisa de las Fuentes, Jiang He, Aldi T. Kraja, Nancy L. Pedersen, Albert V. Smith, Woon-Puay Koh, Bernardo L. Horta, He Gao, Traci M. Bartz, Mike A. Nalls, Federica Laguzzi, Raymond Noordam, Paul M. Ridker, Tien Yin Wong, Patricia B. Munroe, Paul S. de Vries, Adolfo Correa, Maris Alver, Dan E. Arking, Colin A. McKenzie, John M. Starr, Chi Charles Gu, Dongfeng Gu, Stefan Weiss, Patricia A. Peyser, Jessica D. Faul, Xu Chen, Jill M. Norris, Patrik K. E. Magnusson, Tamar Sofer, Ioanna Ntalla, Xiuqing Guo, Paul Elliott, Lawrence F. Bielak, Konstantin Strauch, Xueling Sim, Norihiro Kato, Evangelos Evangelou, Ilja M. Nolte, Steven C. Hunt, Mario Sims, Giorgia Girotto, Chuan Gao, Pamela J. Schreiner, Philippe Froguel, Archie Campbell, Xiao-Ou Shu, Claude Bouchard, Kurt Lohman, David R. Weir, José Eduardo Krieger, Yii-Der Ida Chen, Rainer Rauramaa, Walter Palmas, Cornelia M. van Duijn, James M. Shikany, Michael M. Province, Jennifer A. Smith, Wei Zheng, Xiaofeng Zhu, Jianjun Liu, Ozren Polasek, Alexandre C. Pereira, Diane M. Becker, Kari E. North, Salman M. Tajuddin, Deng Xuan, Leslie J. Raffel, Jie Yao, Astrid Petersmann, Ervin F. Fox, Mark J. Caulfield, Daniel I. Chasman, Jasmin Divers, Claudia P. Cabrera, Rico Rueedi, M. Yldau van der Ende, Carl D. Langefeld, Mika Kähönen, Terrence Forrester, Tangchun Wu, Harold Snieder, Caroline Hayward, Tamara B. Harris, Fang-Chi Hsu, Helen R. Warren, Brenda W.J.H. Penninx, Chiea Chuen Khor, Ruifang Li-Gao, Changwei Li, Sami Heikkinen, Jeffrey R. O'Connell, Christian Gieger, Michele K. Evans, Ching-Yu Cheng, Jingjing Liang, Stephen B. Kritchevsky, Gregory L. Burke, Donald W. Bowden, Alexander Teumer, Marcus Dörr, Alanna C. Morrison, Jian-Min Yuan, Annette Peters, Dennis O. Mook-Kanamori, Pedro Marques-Vidal, Pirjo Komulainen, Lisa R. Yanek, Melanie Waldenberger, Alisa K. Manning, Charles N. Rotimi, Chew-Kiat Heng, Tõnu Esko, Franco Giulianini, Miao Li Chee, Treva Rice, David J. Porteous, Yechiel Friedlander, Bing Yu, Myriam Fornage, Karin Leander, Dina Vojinovic, Sharon L.R. Kardia, Xiaoyin Li, Najaf Amin, Karen Schwander, Thomas T. Perls, Oscar Leonel Rueda-Ochoa, Erin B. Ware, Ya Xing Wang, Sandosh Padmanabhan, H. Janaka de Silva, André G. Uitterlinden, Rajkumar Dorajoo, Bruna Gigante, Jennifer A. Brody, Paolo Gasparini, Maryam Kavousi, Wanqing Wen, Stephen Sidney, Alan B. Zonderman, Michael R. Brown, Tuomo Rankinen, Timo A. Lakka, Yun Ju Sung, Alaitz Poveda, Bruce M. Psaty, Terho Lehtimäki, Tanika N. Kelly, Igor Rudan, Brigitte Kühnel, Christopher P. Nelson, John M. C. Connell, Mickaël Canouil, Niek Verweij, Thomas W. Winkler, Ian J. Deary, Marco Brumat, Yize Li, Fumihiko Takeuchi, Wei Zhao, Andres Metspalu, Marguerite R. Irvin, David C. Liewald, Pim van der Harst, Hugues Aschard, Candace M. Kammerer, Melissa A. Richard, Adesola Ogunniyi, Wen Bin Wei, Morris A. Swertz, Fernando Pires Hartwig, Dabeeru C. Rao, Reedik Mägi, Solomon K. Musani, Mathilde Boissel, Jonathan Marten, Nilesh J. Samani, Amy R. Bentley, Sarah E. Harris, Charumathi Sabanayagam, Mary F. Feitosa, Jost B. Jonas, Andrea R. V. R. Horimoto, Paul W. Franks, E. Shyong Tai, Medical Research Council (MRC), de las Fuentes, L., Sung, Y. J., Noordam, R., Winkler, T., Feitosa, M. F., Schwander, K., Bentley, A. R., Brown, M. R., Guo, X., Manning, A., Chasman, D. I., Aschard, H., Bartz, T. M., Bielak, L. F., Campbell, A., Cheng, C. -Y., Dorajoo, R., Hartwig, F. P., Horimoto, A. R. V. R., Li, C., Li-Gao, R., Liu, Y., Marten, J., Musani, S. K., Ntalla, I., Rankinen, T., Richard, M., Sim, X., Smith, A. V., Tajuddin, S. M., Tayo, B. O., Vojinovic, D., Warren, H. R., Xuan, D., Alver, M., Boissel, M., Chai, J. -F., Chen, X., Christensen, K., Divers, J., Evangelou, E., Gao, C., Girotto, G., Harris, S. E., He, M., Hsu, F. -C., Kuhnel, B., Laguzzi, F., Li, X., Lyytikainen, L. -P., Nolte, I. M., Poveda, A., Rauramaa, R., Riaz, M., Rueedi, R., Shu, X. -O., Snieder, H., Sofer, T., Takeuchi, F., Verweij, N., Ware, E. B., Weiss, S., Yanek, L. R., Amin, N., Arking, D. E., Arnett, D. K., Bergmann, S., Boerwinkle, E., Brody, J. A., Broeckel, U., Brumat, M., Burke, G., Cabrera, C. P., Canouil, M., Chee, M. L., Chen, Y. -D. I., Cocca, M., Connell, J., de Silva, H. J., de Vries, P. S., Eiriksdottir, G., Faul, J. D., Fisher, V., Forrester, T., Fox, E. F., Friedlander, Y., Gao, H., Gigante, B., Giulianini, F., Gu, C. C., Gu, D., Harris, T. B., He, J., Heikkinen, S., Heng, C. -K., Hunt, S., Ikram, M. A., Irvin, M. R., Kahonen, M., Kavousi, M., Khor, C. C., Kilpelainen, T. O., Koh, W. -P., Komulainen, P., Kraja, A. T., Krieger, J. E., Langefeld, C. D., Li, Y., Liang, J., Liewald, D. C. M., Liu, C. -T., Liu, J., Lohman, K. K., Magi, R., Mckenzie, C. A., Meitinger, T., Metspalu, A., Milaneschi, Y., Milani, L., Mook-Kanamori, D. O., Nalls, M. A., Nelson, C. P., Norris, J. M., O'Connell, J., Ogunniyi, A., Padmanabhan, S., Palmer, N. D., Pedersen, N. L., Perls, T., Peters, A., Petersmann, A., Peyser, P. A., Polasek, O., Porteous, D. J., Raffel, L. J., Rice, T. K., Rotter, J. I., Rudan, I., Rueda-Ochoa, O. -L., Sabanayagam, C., Salako, B. L., Schreiner, P. J., Shikany, J. M., Sidney, S. S., Sims, M., Sitlani, C. M., Smith, J. A., Starr, J. M., Strauch, K., Swertz, M. A., Teumer, A., Tham, Y. C., Uitterlinden, A. G., Vaidya, D., van der Ende, M. Y., Waldenberger, M., Wang, L., Wang, Y. -X., Wei, W. -B., Weir, D. R., Wen, W., Yao, J., Yu, B., Yu, C., Yuan, J. -M., Zhao, W., Zonderman, A. B., Becker, D. M., Bowden, D. W., Deary, I. J., Dorr, M., Esko, T., Freedman, B. I., Froguel, P., Gasparini, P., Gieger, C., Jonas, J. B., Kammerer, C. M., Kato, N., Lakka, T. A., Leander, K., Lehtimaki, T., Magnusson, P. K. E., Marques-Vidal, P., Penninx, B. W. J. H., Samani, N. J., van der Harst, P., Wagenknecht, L. E., Wu, T., Zheng, W., Zhu, X., Bouchard, C., Cooper, R. S., Correa, A., Evans, M. K., Gudnason, V., Hayward, C., Horta, B. L., Kelly, T. N., Kritchevsky, S. B., Levy, D., Palmas, W. R., Pereira, A. C., Province, M. M., Psaty, B. M., Ridker, P. M., Rotimi, C. N., Tai, E. S., van Dam, R. M., van Duijn, C. M., Wong, T. Y., Rice, K., Gauderman, W. J., Morrison, A. C., North, K. E., Kardia, S. L. R., Caulfield, M. J., Elliott, P., Munroe, P. B., Franks, P. W., Rao, D. C., Fornage, M., Washington University in Saint Louis (WUSTL), Leiden University Medical Center (LUMC), University of Regensburg, Washington University School of Medicine in St. Louis, National Institutes of Health [Bethesda] (NIH), Harbor UCLA Medical Center [Torrance, Ca.], Massachusetts General Hospital [Boston], Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Harvard School of Public Health, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), The University of Texas Health Science Center at Houston (UTHealth), Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Digital Health, Universiteit Leiden, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Lifelines Cohort Study, Epidemiology, Radiology & Nuclear Medicine, Internal Medicine, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), and Cardiovascular Centre (CVC)
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0301 basic medicine ,CORONARY-HEART-DISEASE ,SOCIOECONOMIC-STATUS ,RISK-FACTORS ,CARDIOVASCULAR-DISEASE ,ESSENTIAL-HYPERTENSION ,C825T POLYMORPHISM ,SOCIAL-CLASS ,ASSOCIATION ,EXPRESSION ,VARIANTS ,Blood Pressure ,Genome ,0302 clinical medicine ,11 Medical and Health Sciences ,Genetics ,Psychiatry ,[STAT.AP]Statistics [stat]/Applications [stat.AP] ,17 Psychology and Cognitive Sciences ,Psychiatry and Mental health ,Meta-analysis ,Hypertension ,[STAT.ME]Statistics [stat]/Methodology [stat.ME] ,Life Sciences & Biomedicine ,GNB3 ,Biochemistry & Molecular Biology ,Biology ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Lifelines Cohort Study ,SDG 3 - Good Health and Well-being ,Humans ,Risk factor ,Molecular Biology ,Gene ,Science & Technology ,Neurosciences ,Epistasis, Genetic ,06 Biological Sciences ,Genetic architecture ,Educational attainment ,030104 developmental biology ,Blood pressure ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Genetic Loci ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Neurosciences & Neurology ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,Blood Pressure/genetics ,Genome-Wide Association Study ,Hypertension/genetics ,030217 neurology & neurosurgery - Abstract
Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10 -8 ). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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- 2020
9. Trans-ethnic analysis of metabochip data identifies two new loci associated with BMI.
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Gong J, Nishimura KK, Fernandez-Rhodes L, Haessler J, Bien S, Graff M, Lim U, Lu Y, Gross M, Fornage M, Yoneyama S, Isasi CR, Buzkova P, Daviglus M, Lin DY, Tao R, Goodloe R, Bush WS, Farber-Eger E, Boston J, Dilks HH, Ehret G, Gu CC, Lewis CE, Nguyen KH, Cooper R, Leppert M, Irvin MR, Bottinger EP, Wilkens LR, Haiman CA, Park L, Monroe KR, Cheng I, Stram DO, Carlson CS, Jackson R, Kuller L, Houston D, Kooperberg C, Buyske S, Hindorff LA, Crawford DC, Loos RJF, Le Marchand L, Matise TC, North KE, and Peters U
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- Genome-Wide Association Study, Genomics, Humans, Polymorphism, Single Nucleotide genetics, Body Mass Index, Racial Groups genetics, Racial Groups statistics & numerical data
- Abstract
Objective: Body mass index (BMI) is commonly used to assess obesity, which is associated with numerous diseases and negative health outcomes. BMI has been shown to be a heritable, polygenic trait, with close to 100 loci previously identified and replicated in multiple populations. We aim to replicate known BMI loci and identify novel associations in a trans-ethnic study population., Subjects: Using eligible participants from the Population Architecture using Genomics and Epidemiology consortium, we conducted a trans-ethnic meta-analysis of 102 514 African Americans, Hispanics, Asian/Native Hawaiian, Native Americans and European Americans. Participants were genotyped on over 200 000 SNPs on the Illumina Metabochip custom array, or imputed into the 1000 Genomes Project (Phase I). Linear regression of the natural log of BMI, adjusting for age, sex, study site (if applicable), and ancestry principal components, was conducted for each race/ethnicity within each study cohort. Race/ethnicity-specific, and combined meta-analyses used fixed-effects models., Results: We replicated 15 of 21 BMI loci included on the Metabochip, and identified two novel BMI loci at 1q41 (rs2820436) and 2q31.1 (rs10930502) at the Metabochip-wide significance threshold (P<2.5 × 10
- 7 ). Bioinformatic functional investigation of SNPs at these loci suggests a possible impact on pathways that regulate metabolism and adipose tissue., Conclusion: Conducting studies in genetically diverse populations continues to be a valuable strategy for replicating known loci and uncovering novel BMI associations.- Published
- 2018
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10. A DNA methylation biomarker of alcohol consumption.
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Liu C, Marioni RE, Hedman ÅK, Pfeiffer L, Tsai PC, Reynolds LM, Just AC, Duan Q, Boer CG, Tanaka T, Elks CE, Aslibekyan S, Brody JA, Kühnel B, Herder C, Almli LM, Zhi D, Wang Y, Huan T, Yao C, Mendelson MM, Joehanes R, Liang L, Love SA, Guan W, Shah S, McRae AF, Kretschmer A, Prokisch H, Strauch K, Peters A, Visscher PM, Wray NR, Guo X, Wiggins KL, Smith AK, Binder EB, Ressler KJ, Irvin MR, Absher DM, Hernandez D, Ferrucci L, Bandinelli S, Lohman K, Ding J, Trevisi L, Gustafsson S, Sandling JH, Stolk L, Uitterlinden AG, Yet I, Castillo-Fernandez JE, Spector TD, Schwartz JD, Vokonas P, Lind L, Li Y, Fornage M, Arnett DK, Wareham NJ, Sotoodehnia N, Ong KK, van Meurs JBJ, Conneely KN, Baccarelli AA, Deary IJ, Bell JT, North KE, Liu Y, Waldenberger M, London SJ, Ingelsson E, and Levy D
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- Adult, Aged, Alcohol Drinking metabolism, Alcohol-Related Disorders metabolism, Biomarkers blood, Black People genetics, CpG Islands genetics, Epigenesis, Genetic, Ethanol blood, Ethanol metabolism, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, White People genetics, Alcohol Drinking genetics, Alcohol-Related Disorders genetics, DNA Methylation drug effects
- Abstract
The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (n
total =13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10-7 . Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10-7 . In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.- Published
- 2018
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11. CPT1A methylation is associated with plasma adiponectin.
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Aslibekyan S, Do AN, Xu H, Li S, Irvin MR, Zhi D, Tiwari HK, Absher DM, Shuldiner AR, Zhang T, Chen W, Tanner K, Hong C, Mitchell BD, Berenson G, and Arnett DK
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- Adult, Black or African American genetics, CpG Islands, Cross-Sectional Studies, Epigenomics methods, Female, Genetic Association Studies, Genotype, Humans, Male, Middle Aged, Phenotype, Proteins genetics, United States epidemiology, White People genetics, Adiponectin blood, Carnitine O-Palmitoyltransferase genetics, DNA Methylation, Epigenesis, Genetic
- Abstract
Background and Aims: Adiponectin, an adipose-secreted protein that has been linked to insulin sensitivity, plasma lipids, and inflammatory patterns, is an established biomarker for metabolic health. Despite clinical relevance and high heritability, the determinants of plasma adiponectin levels remain poorly understood., Methods and Results: We conducted the first epigenome-wide cross-sectional study of adiponectin levels using methylation data on 368,051 cytosine-phosphate-guanine (CpG) sites in CD4+ T-cells from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n = 991). We fit linear mixed models, adjusting for age, sex, study site, T-cell purity, and family. We have identified a positive association (regression coefficient ± SE = 0.01 ± 0.001, P = 3.4 × 10
-13 ) between plasma adiponectin levels and methylation of a CpG site in CPT1A, a key player in fatty acid metabolism. The association was replicated (n = 474, P = 0.0009) in whole blood samples from the Amish participants of the Heredity and Phenotype Intervention (HAPI) Heart Study as well as White (n = 592, P = 0.0005) but not Black (n = 243, P = 0.18) participants of the Bogalusa Heart Study (BHS). The association remained significant upon adjusting for BMI and smoking in GOLDN and HAPI but not BHS. We also identified associations between methylation loci in RNF145 and UFM1 and plasma adiponectin in GOLDN and White BHS participants, although the association was not robust to adjustment for BMI or smoking., Conclusion: We have identified and replicated associations between several biologically plausible loci and plasma adiponectin. These findings support the importance of epigenetic processes in metabolic traits, laying the groundwork for future translational applications., (Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)- Published
- 2017
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12. Hemostasis biomarkers and risk of sepsis: the REGARDS cohort.
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Moore JX, Zakai NA, Mahalingam M, Griffin RL, Irvin MR, Safford MM, Baddley JW, and Wang HE
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- Aged, Aged, 80 and over, Biomarkers metabolism, Case-Control Studies, Cohort Studies, Ethnicity, Factor IX metabolism, Factor XI metabolism, Female, Fibrinogen metabolism, Hospitalization, Humans, Male, Middle Aged, Models, Biological, Regression Analysis, Sepsis epidemiology, United States, Hemostasis, Sepsis blood, Sepsis physiopathology
- Abstract
Essentials Few studies have investigated the risk of sepsis by baseline hemostasis biomarkers measures. Baseline hemostasis biomarkers and risk of sepsis was examined using case-control study design. Increased fibrinogen, factor IX, and factor XI levels may be associated with risk of sepsis. Hemostasis biomarkers may provide a target for sepsis mitigation or prevention., Summary: Background Sepsis is a major public health concern, responsible for more than 750 000 hospitalizations and 200 000 annual deaths in the USA. Few studies have investigated the association between baseline measurements of hemostasis biomarkers and the future risk of sepsis. Objective To determine whether hemostasis biomarkers levels measured at baseline in a cohort of community-dwelling participants are associated with the risk of future sepsis events. Methods We performed a nested case-control study within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. We identified sepsis hospitalizations occurring over a 10-year period. There were 50 incident sepsis cases with baseline measurements of hemostasis (fibrinogen, factor VIII, FIX, FXI, protein C, and D-dimer). Using incidence density sampling, we matched the 50 sepsis cases with 200 controls by age, sex, and race. We used conditional logistic regression to evaluate the association between baseline hemostasis biomarkers and future sepsis events. Results Comparison of 50 sepsis cases with 200 non-sepsis controls showed that sepsis cases had lower education and income, were more likely to live in the stroke belt, had chronic lung disease, and had higher albumin level/creatinine level ratios (ACRs). Individuals with higher baseline fibrinogen levels (adjusted odds ratio [OR] per standard deviation: 1.40, 95% confidence interval [CI] 1.01-1.94), FIX levels ([OR] 1.46, 95% [CI] 1.03-2.07) and FXI levels ([OR]1.52, 95% [CI] 1.04-2.23) were more likely to experience a sepsis event. Conclusion Baseline fibrinogen, FIX and FXI levels are associated with future episodes of sepsis. Hemostasis biomarkers may provide targets for sepsis mitigation or prevention., (© 2016 International Society on Thrombosis and Haemostasis.)
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- 2016
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13. Preliminary evidence of genetic determinants of adiponectin response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network.
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Aslibekyan S, An P, Frazier-Wood AC, Kabagambe EK, Irvin MR, Straka RJ, Tiwari HK, Tsai MY, Hopkins PN, Borecki IB, Ordovas JM, and Arnett DK
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- Adiponectin metabolism, Adipose Tissue, White drug effects, Adipose Tissue, White metabolism, Adult, Cadherins metabolism, Female, Gene Frequency, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Middle Aged, Minnesota, Oligonucleotide Array Sequence Analysis, Siblings, Utah, Adiponectin blood, Cadherins genetics, Chromosomes, Human, Pair 12, Drug Resistance, Fenofibrate pharmacology, Hypolipidemic Agents pharmacology, Polymorphism, Single Nucleotide
- Abstract
Background and Aims: Adiponectin is an adipose-secreted protein that has been linked to changes in insulin sensitivity, high-density lipoprotein cholesterol levels, and inflammatory patterns. Although fenofibrate therapy can raise adiponectin levels, treatment response is heterogeneous and heritable, suggesting a role for genetic mediators. This is the first genome-wide association study of fenofibrate effects on circulating adiponectin., Methods and Results: Plasma adiponectin was measured in participants of the Genetics of Lipid Lowering Drugs and Diet Network (n = 793) before and after a 3-week daily treatment with 160 mg of fenofibrate. Associations between variants on the Affymetrix Genome-Wide Human SNP Array 6.0 and adiponectin were assessed using mixed linear models, adjusted for age, sex, site, and family. We observed a statistically significant (P = 5 × 10⁻⁸) association between rs2384207 in 12q24, a region previously linked to several metabolic traits, and the fenofibrate-induced change in circulating adiponectin. Additionally, our genome-wide analysis of baseline adiponectin levels replicated the previously reported association with CDH13 and suggested novel associations with markers near the PCK1, ZBP1, TMEM18, and SCUBE1 genes. The findings from the single marker tests were corroborated in gene-based analyses. Biological pathway analyses suggested a borderline significant association between the EGF receptor signaling pathway and baseline adiponectin levels., Conclusions: We present preliminary evidence linking several biologically relevant genetic variants to adiponectin levels at baseline and in response to fenofibrate therapy. Our findings provide support for fine-mapping of the 12q24 region to investigate the shared biological mechanisms underlying levels of circulating adiponectin and susceptibility to metabolic disease., (Copyright © 2012 Elsevier B.V. All rights reserved.)
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- 2013
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14. Whole-exome sequencing and an iPSC-derived cardiomyocyte model provides a powerful platform for gene discovery in left ventricular hypertrophy.
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Zhi D, Irvin MR, Gu CC, Stoddard AJ, Lorier R, Matter A, Rao DC, Srinivasasainagendra V, Tiwari HK, Turner A, Broeckel U, and Arnett DK
- Abstract
Rationale: Left ventricular hypertrophy (LVH) is a heritable predictor of cardiovascular disease, particularly in blacks., Objective: Determine the feasibility of combining evidence from two distinct but complementary experimental approaches to identify novel genetic predictors of increased LV mass., Methods: Whole-exome sequencing (WES) was conducted in seven African-American sibling trios ascertained on high average familial LV mass indexed to height (LVMHT) using Illumina HiSeq technology. Identified missense or nonsense (MS/NS) mutations were examined for association with LVMHT using linear mixed models adjusted for age, sex, body weight, and familial relationship. To functionally assess WES findings, human induced pluripotent stem cell-derived cardiomyocytes (induced pluripotent stem cell-CM) were stimulated to induce hypertrophy; mRNA sequencing (RNA-seq) was used to determine gene expression differences associated with hypertrophy onset. Statistically significant findings under both experimental approaches identified LVH candidate genes. Candidate genes were further prioritized by seven supportive criteria that included additional association tests (two criteria), regional linkage evidence in the larger HyperGEN cohort (one criterion), and publically available gene and variant based annotations (four criteria)., Results: WES reads covered 91% of the target capture region (of size 37.2 MB) with an average coverage of 65×. WES identified 31,426 MS/NS mutations among the 21 individuals. A total of 295 MS/NS variants in 265 genes were associated with LVMHT with q-value <0.25. Of the 265 WES genes, 44 were differentially expressed (P < 0.05) in hypertrophied cells. Among the 44 candidate genes identified, 5, including HLA-B, HTT, MTSS1, SLC5A12, and THBS1, met 3 of 7 supporting criteria. THBS1 encodes an adhesive glycoprotein that promotes matrix preservation in pressure-overload LVH. THBS1 gene expression was 34% higher in hypertrophied cells (P = 0.0003) and a predicted conserved and damaging NS variant in exon 13 (A2099G) was significantly associated with LVHMT (P = 4 × 10(-6))., Conclusion: Combining evidence from cutting-edge genetic and cellular experiments can enable identification of novel LVH risk loci.
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- 2012
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15. Genetic risk factors for type 2 diabetes with pharmacologic intervention in African-American patients with schizophrenia or schizoaffective disorder.
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Irvin MR, Wiener HW, Perry RP, Savage RM, and Go RC
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- Adult, Aged, Calpain genetics, Family Health, Female, Genetics, Population, Genome-Wide Association Study, Humans, Male, Middle Aged, Odds Ratio, Pharmacogenetics, Phosphoric Diester Hydrolases genetics, Polymorphism, Single Nucleotide genetics, Psychotic Disorders genetics, Pyrophosphatases genetics, Risk Factors, Schizophrenia genetics, TCF Transcription Factors genetics, Transcription Factor 7-Like 2 Protein, Black or African American genetics, Antipsychotic Agents adverse effects, Antipsychotic Agents therapeutic use, Diabetes Mellitus, Type 2 chemically induced, Diabetes Mellitus, Type 2 genetics, Genetic Predisposition to Disease, Psychotic Disorders drug therapy, Schizophrenia drug therapy
- Abstract
An increased prevalence of type 2 diabetes (T2D) in schizophrenia (SCZ) patients has been observed. Exposure to antipsychotics (APs) has been shown to induce metabolic dysregulation in some patients but not all treated patients. We hypothesized that important candidate genes for T2D may increase risk for T2D in African-American patients with SCZ or schizoaffective disorder. The PAARTNERS study comprises African-American families with at least one proband with SCZ or schizoaffective disorder. The current study of PAARTNERS SCZ and schizoaffective disorder cases (N=820) examined single nucleotide polymorphisms (SNPs) within select T2D candidate genes including transcription factor 7-like 2 (TCF7L2), calpain 10 (CAPN10), and ectoenzyme nucleotide pyrophosphatase phosphodiesterase 1 (ENNP1) for association with prevalent T2D. We report the association of TCF7L2 (rs7903146) with T2D under both additive and recessive models for the risk allele T. Specifically, the odds ratio (OR) for having T2D was 1.4 (p=0.03) under an additive model and 2.4 (p=0.004) under a recessive model. We also report a marginally significant TCF7L2 by AP treatment interaction that should be investigated in future studies. CAPN10 (rs3792267) was marginally associated with T2D with OR=1.5 (p=0.08) when considering the model GG vs. AG/AA with risk allele G. ENPP1 (rs1044498) was not associated with T2D. We conclude TCF7L2, a risk factor for T2D in the general population, is also a risk factor for T2D in African-American patients with SCZ or schizoaffective disorder. Research is needed to determine if T2D associated polymorphisms are of interest in the pharmacogenetics and future treatment choices of antipsychotics in African-American patients.
- Published
- 2009
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