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Christopher O'Donnell, M.D., M.P.H.

Christopher O'Donnell, M.D., M.P.H.
Senior Investigator


Building PERINI Room SUITE 2
73 Mt Wayte Ave
Framingham, MA 01702
P: +1 508 935 3435
odonnellc@nhlbi.nih.gov

Background

Dr. Christopher O’Donnell received his A.B. in biochemistry from Brown University in 1983, his M.D. from Harvard Medical School in 1987, and his M.P.H. from the Harvard School of Public Health in 1994. He conducted his internship and residency in internal medicine at Massachusetts General Hospital in Boston from 1987 to 1990, then completed a clinical research fellowship in cardiology at Massachusetts General from 1991 to 1994. Dr. O’Donnell joined the NHLBI’s Framingham Heart Study (FHS) as a Medical Officer in 1996, and became associate director of the FHS in 2001. In 2006, he was appointed Senior Advisor to the Director of NHLBI for Genome Research, and became a tenured Senior Investigator 2007. Dr. O’Donnell also continues to hold academic appointments at Massachusetts General Hospital and Harvard Medical School. He has received several NIH/NHLBI awards for his genomics research and work with the FHS, and he is also an elected member of the American Society for Clinical Investigation. In addition, Dr. O’Donnell is a fellow of the American College of Cardiology, a silver heart member of the American Heart Association, and a member of the American Society of Human Genetics. He has published over 380 original scientific articles, reviews, editorials, and book chapters.

Research Interests

Both genetics and environment contribute to the development of cardiovascular disease (CVD), and in particular there is strong evidence for an important heritable component to CVD and its risk factors. Dr. O’Donnell’s research aims to discover the genetic and genomic determinants of CVD as well as their functional underpinnings. In particular, Dr. O’Donnell is interested in the genetic determinants of subclinical CVD, atherosclerotic CVD risk factors, and clinical coronary heart disease.

Dr. O’Donnell’s group is currently conducting several genomewide association studies (GWAS) as well as genomewide DNA and RNA sequencing studies to identify the specific genes and genetic variants underlying subclinical vascular disease (coronary and aortic atherosclerosis, carotid artery intimal medial thickness, and aortic valve disease), hemostatic/thrombosis factor levels, and clinically apparent CVD, (myocardial infarction). His group combines genetic studies with high resolution phenotypic measurements, including medical imaging such as computed tomography or ultrasound, to measure both clinical and subclinical traits. The laboratory for these important investigations is the longstanding Framingham Heart Study, for which Dr. O’Donnell serves as chair of the Framingham Genetic Steering Committee. He has provided senior leadership in several large, collaborative population-based consortia, including the Framingham Heart Study SNP Health Association (SHARe) Program, the international Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, and the NHLBI Exome Sequencing Project.

In recent years, his group and collaborators have reported the discovery of dozens of novel genetic loci underlying CVD traits and associated disease risk. Among these findings include a set of genetic loci that affect carotid intima-media thickness and a lipoprotein(a) variant that doubles the risk of calcification in the aortic valve. Another recent study involved a thorough sequencing and characterization of the CVD-associated 9p21.3 locus in the Framingham Heart Study; this robust study found strong genetic associations in this locus for myocardial infarction risk, elevated coronary artery calcium, and larger abdominal aorta diameters, but no evidence for association with traditional CVD risk factors. He is a key collaborator in the international CARDIoGRAM Plus C4D Consortium investigations that have uncovered over 45 genetic loci underlying myocardial infarction.

Looking forward, Dr. O’Donnell and his group are extending these current studies by diving deeper into the functional genetics/genomics using new approaches, including exome chip genotyping as well as whole genome DNA and RNA sequencing. Work underway now is aimed at detailed studies in specific tissues from humans and model organisms to discover the causal mechanisms of DNA variant associations with CVD. An exciting novel direction within the Framingham Heart Study, in collaboration with Harvard University, is the creation of a large resource of induced pluripotent stem cells from Framingham Heart Study research participants for the purpose of future functional genomic studies. Critically, all the data, genetic results, and tools are being shared with the scientific community with the ultimate objective of rapid facilitation of clinical translation. It is hoped that the resulting discoveries will lead to improved “personalized” approaches to predicting, treating, and preventing CVD in patients, families, and the population.

Selected Publications

Genetic associations with valvular calcification and aortic stenosis.
Thanassoulis G, Campbell CY, Owens DS, Smith JG, Smith AV, Peloso GM, Kerr KF, Pechlivanis S, Budoff MJ, Harris TB, Malhotra R, O'Brien KD, Kamstrup PR, Nordestgaard BG, Tybjaerg-Hansen A, Allison MA, Aspelund T, Criqui MH, Heckbert SR, Hwang SJ, Liu Y, Sjogren M, van der Pals J, Kälsch H, Mühleisen TW, Nöthen MM, Cupples LA, Caslake M, Di Angelantonio E, Danesh J, Rotter JI, Sigurdsson S, Wong Q, Erbel R, Kathiresan S, Melander O, Gudnason V, O'Donnell CJ, Post WS.
N Engl J Med. 2013 Feb 7;368(6):503-12.
[Text Abstract on PubMed]

Resequencing and Clinical Associations of the 9p21.3 Region: A Comprehensive Investigation in the Framingham Heart Study.
Johnson AD, Hwang SJ, Voorman A, Morrison A, Peloso GM, Hu YH, Thanassoulis G, Newton-Cheh C, Rogers IS, Hoffman U, Freedman JE, Fox CS, Psaty BM, Boerwinkle E, Cupples LA, O'Donnell CJ.
Circulation. 2013 Jan 11.
[Text Abstract on PubMed]

Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction.
O'Donnell CJ, Kavousi M, Smith AV, Kardia SL, Feitosa MF, Hwang SJ, Sun YV, Province MA, Aspelund T, Dehghan A, Hoffmann U, Bielak LF, Zhang Q, Eiriksdottir G, van Duijn CM, Fox CS, de Andrade M, Kraja AT, Sigurdsson S, Elias-Smale SE, Murabito JM, Launer LJ, van der Lugt A, Kathiresan S, CARDIoGRAM Consortium, Krestin GP, Herrington DM, Howard TD, Liu Y, Post W, Mitchell BD, O'Connell JR, Shen H, Shuldiner AR, Altshuler D, Elosua R, Salomaa V, Schwartz SM, Siscovick DS, Voight BF, Bis JC, Glazer NL, Psaty BM, Boerwinkle E, Heiss G, Blankenberg S, Zeller T, Wild PS, Schnabel RB, Schillert A, Ziegler A, Münzel TF, White CC, Rotter JI, Nalls M, Oudkerk M, Johnson AD, Newman AB, Uitterlinden AG, Massaro JM, Cunningham J, Harris TB, Hofman A, Peyser PA, Borecki IB, Cupples LA, Gudnason V, Witteman JC.
Circulation. 2011 Dec 20;124(25):2855-64.
[Text Abstract on PubMed]

Genomics of cardiovascular disease.
O'Donnell CJ, Nabel EG.
N Engl J Med. 2011 Dec 1;365(22):2098-109.
[Text Abstract on PubMed]

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque.
Bis JC, Kavousi M, Franceschini N, Isaacs A, Abecasis GR, Schminke U, Post WS, Smith AV, Cupples LA, Markus HS, Schmidt R, Huffman JE, Lehtimäki T, Baumert J, Münzel T, Heckbert SR, Dehghan A, North K, Oostra B, Bevan S, Stoegerer EM, Hayward C, Raitakari O, Meisinger C, Schillert A, Sanna S, Völzke H, Cheng YC, Thorsson B, Fox CS, Rice K, Rivadeneira F, Nambi V, Halperin E, Petrovic KE, Peltonen L, Wichmann HE, Schnabel RB, Dörr M, Parsa A, Aspelund T, Demissie S, Kathiresan S, Reilly MP, Taylor K, Uitterlinden A, Couper DJ, Sitzer M, Kähönen M, Illig T, Wild PS, Orru M, Lüdemann J, Shuldiner AR, Eiriksdottir G, White CC, Rotter JI, Hofman A, Seissler J, Zeller T, Usala G, Ernst F, Launer LJ, D'Agostino, O'Leary DH, Ballantyne C, Thiery J, Ziegler A, Lakatta EG, Chilukoti RK, Harris TB, Wolf PA, Psaty BM, Polak JF, Li X, Rathmann W, Uda M, Boerwinkle E, Klopp N, Schmidt H, Wilson JF, Viikari J, Koenig W, Blankenberg S, Newman AB, Witteman J, Heiss G, Duijn Cv, Scuteri A, Homuth G, Mitchell BD, Gudnason V, O'Donnell CJ, CARDIoGRAM Consortium.
Nat. Genet. 2011 Oct;43(10):940-7.
[Text Abstract on PubMed]

Christopher O'Donnell's Full List of Publications

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Last Updated: February 04, 2014