Arking, Dan - Johns Hopkins University

个人简介

Dr. Dan Arking is an Associate Professor of Medicine at the McKusick-Nathans Institute of Genetic Medicine. He studies genetics of complex disease, cardiovascular disease and sudden cardiac death, autism and development and implementation of novel GWAS analytical tools. Dr. Arking received a bachelor’s degree from the University of Maryland in College Park and a PhD from the Johns Hopkins University School of Medicine before joining the faculty. He is a member of the American Society for Human Genetics, the Association for the Eradication of Heart Attack, and the Simons Foundation Autism Research Gene Advisory Board. B.S., University of Maryland (College Park) (Maryland) (1995) Ph.D., Johns Hopkins University School of Medicine (Maryland) (2002)

研究领域

My research focuses on genomics of complex human disease, with the primary goal of identifying and characterizing genetics variants that modify risk for human disease. Traditional approaches to identify genes involved in complex disease have relied upon screening candidate genes or family-based linkage studies in families with rare monogenic forms of disease. Given the limited success of these approaches to identify genes contributing to common disease, our group has pioneered the use of genome-wide association studies (GWAS), which allow for an unbiased screen of virtually all common genetic variants in the genome. We are currently developing improved GWAS methodology, as well as exploring the integration of additional genome level data (RNA expression, DNA methylation, protein expression) to improve the power to identify genetic influences of disease. My lab is actively involved in researching autism, a childhood neuropsychiatric disorder, as well as cardiovascular genomics, with a focus on sudden cardiac death (SCD). Autism is a devastating neuropsychiatric condition with unknown pathophysiology. Autism spectrum disorders (ASD) have an estimated incidence of 1/200 and thus are more common than many other childhood disorders. Although ASD have a multifactorial etiology, it has a large genetic component, and it is becoming clear that comprehensive efforts involving large sample sizes and methods to reduce heterogeneity are necessary. Our group has demonstrated that common sequence changes in the CNTNAP2 and SEMA5A genes are associated with altered risk for ASD. For both these genes, we have been able to demonstrate that gene expression is altered in brains obtained from autism patients relative to age- and sex-matched controls. To identify additional genetic variants, we are performing a comprehensive and integrative screen of autism brains and matched controls, including genetic variation, methylation profiling, and gene expression. SCD is one of the leading causes of death in the United States, with ~462,000 of the 2,400,000 (19.3%) US deaths in 1999 classified as SCDs. From the standpoint of preventive care, SCD poses a huge burden since less than 10% of SCD victims survive, and approximately 2/3 of SCD victims do not have clinical symptoms that would warrant preventive intervention. Thus, the use of genetics to identify individuals who are at high risk for SCD is crucial. As a further complication, limited DNA resources are available for individuals who experience SCD due to the low survival rate. We are working to expand the number of available SCD cases, and in addition are collecting hearts from SCD victims for gene expression, DNA methylation, and protein expression profiling. In addition to directly identifying genes for SCD, we are examining intermediate quantitative traits, such as the QT interval, a measure of cardiac repolarization associated with SCD, as well as other ECG parameters. Elucidating the genetic basis of electrical activity in the heart is likely to be a critical component to understanding SCD risk. Additional work ongoing in my lab is focused on identifying genes involved in frailty/aging, with a particular focus on the role of mitochondria in longevity.

近期论文

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Maitra A*, Arking DE* , Shivapurkar N, Ikeda M, Stastny V, Kassauei K, Sui G, Cutler DJ, Liu Y, Brimble SN, Noaksson K, Hyllner J, Schulz TC, Zeng X, Freed WJ, Crook J, Abraham S, Colman A, Sartipy P, Matsui S, Carpenter M, Gazdar AF, Rao M, Chakravarti A. Genomic Alterations in Cultured Human Embryonic Stem Cells. Nat Genet. 2005; 37(10):1099-103. *These authors contributed equally to the work. Arking DE* , Pfeufer A*, Post W, Kao WH, Newton-Cheh C, Ikeda M, West K, Kashuk C, Akyol M, Perz S, Jalilzadeh S, Illig T, Gieger C, Guo CY, Larson MG, Wichmann HE, Marbán E, O'Donnell CJ, Hirschhorn JN, Kääb S, Spooner PM, Meitinger T, Chakravarti A. A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization. Nat Genet. 2006; 38(6):644-651. *These authors contributed equally to the work. Arking DE , Cutler DJ, Brune CW, Teslovich TM, West K, Ikeda M, Rea A, Guy M, Lin S, Cook EH, Chakravarti A. A common genetic variant in the neurexin-superfamily member CNTNAP2 increases familial risk of autism. Am J Hum Genet. 2008; 82(1): 160-4. Weiss LA, Shen Y, Korn JM, Arking DE , Miller DT, Fossdal R, Saemundsen E, Stefansson H, Ferreira MA, Green T, Platt OS, Ruderfer DM, Walsh CA, Altshuler D, Chakravarti A, Tanzi RE, Stefansson K, Santangelo SL, Gusella JF, Sklar P, Wu BL, Daly MJ; Autism Consortium. Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med. 2008; 358(7):667-75. Kao WH*, Arking DE* , Post W*, Rea TD, Sotoodehnia N, Prineas RJ, Bishe B, Doan BQ, Boerwinkle E, Psaty BM, Tomaselli GF, Coresh J, Siscovick DS, Marbán E, Spooner PM, Burke GL, Chakravarti A. Genetic variations in nitric oxide synthase 1 adaptor protein are associated with sudden cardiac death in US white community-based populations. Circulation. 2009; 119(7):940-51. *These authors contributed equally to the work. Pfeufer A*, Sanna S*, Arking DE* , Müller M, Gateva V, Fuchsberger C, Ehret GB, Orrú M, Pattaro C, Köttgen A, Perz S, Usala G, Barbalic M, Li M, Pütz B, Scuteri A, Prineas RJ, Sinner MF, Gieger C, Najjar SS, Kao WH, Mühleisen TW, Dei M, Happle C, Möhlenkamp S, Crisponi L, Erbel R, Jöckel KH, Naitza S, Steinbeck G, Marroni F, Hicks AA, Lakatta E, Müller-Myhsok B, Pramstaller PP, Wichmann HE, Schlessinger D, Boerwinkle E, Meitinger T, Uda M, Coresh J, Kääb S, Abecasis GR, Chakravarti A. Common variants at ten loci modulate the QT interval duration in the QTSCD study. Nat Genet. 2009; 41(4):407-14. *These authors contributed equally to the work. Arking DE, Chakravarti A. Understanding cardiovascular disease through the lens of genome-wide association studies. Trends Genet. 2009; 25(9):387-94. Benjamin EJ*, Rice KM*, Arking DE* , Pfeufer A*, van Noord C*, Smith AV*, Schnabel RB, Bis JC, Boerwinkle E, Sinner MF, Dehghan A, Lubitz SA, D'Agostino RB Sr, Lumley T, Ehret GB, Heeringa J, Aspelund T, Newton-Cheh C, Larson MG, Marciante KD, Soliman EZ, Rivadeneira F, Wang TJ, Eiríksdottir G, Levy D, Psaty BM, Li M, Chamberlain AM, Hofman A, Vasan RS, Harris TB, Rotter JI, Kao WH, Agarwal SK, Stricker BH, Wang K, Launer LJ, Smith NL, Chakravarti A, Uitterlinden AG, Wolf PA, Sotoodehnia N, Köttgen A, van Duijn CM, Meitinger T, Mueller M, Perz S, Steinbeck G, Wichmann HE, Lunetta KL, Heckbert SR, Gudnason V, Alonso A, Kääb S, Ellinor PT, Witteman JC. Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry. Nat Genet. 2009; 41(8):879-81 . *These authors contributed equally to the work. Weiss LA*, Arking DE* ; Gene Discovery Project of Johns Hopkins & the Autism Consortium, Daly MJ, Chakravarti A. A genome-wide linkage and association scan reveals novel loci for autism. Nature 2009 Oct 8; 461(7265):802-8. *These authors contributed equally to the work. Pfeufer A*, van Noord C*, Marciante KD*, Arking DE* , Larson MG*, Smith AV*, Tarasov KV*, Müller M, Sotoodehnia N, Sinner MF, Verwoert GC, Li M, Kao WH, Köttgen A, Coresh J, Bis JC, Psaty BM, Rice K, Rotter JI, Rivadeneira F, Hofman A, Kors JA, Stricker BH, Uitterlinden AG, van Duijn CM, Beckmann BM, Sauter W, Gieger C, Lubitz SA, Newton-Cheh C, Wang TJ, Magnani JW, Schnabel RB, Chung MK, Barnard J, Smith JD, Van Wagoner DR, Vasan RS, Aspelund T, Eiriksdottir G, Harris TB, Launer LJ, Najjar SS, Lakatta E, Schlessinger D, Uda M, Abecasis GR, Müller-Myhsok B, Ehret GB, Boerwinkle E, Chakravarti A, Soliman EZ, Lunetta KL, Perz S, Wichmann HE, Meitinger T, Levy D, Gudnason V*, Ellinor PT*, Sanna S*, Kääb S*, Witteman JC*, Alonso A*, Benjamin EJ*, Heckbert SR*. Genome-wide association study of PR interval. Nat Genet 2010; 42(2):153-9. *These authors contributed equally to the work. Ellinor PT*, Lunetta KL*, Glazer NL*, Pfeufer A*, Alonso A*, Chung MK*, Sinner MF*, de Bakker PI, Mueller M, Lubitz SA, Fox E, Darbar D, Smith NL, Smith JD, Schnabel RB, Soliman EZ, Rice KM, Van Wagoner DR, Beckmann BM, van Noord C, Wang K, Ehret GB, Rotter JI, Hazen SL, Steinbeck G, Smith AV, Launer LJ, Harris TB, Makino S, Nelis M, Milan DJ, Perz S, Esko T, Köttgen A, Moebus S, Newton-Cheh C, Li M, Möhlenkamp S, Wang TJ, Kao WH, Vasan RS, Nöthen MM, MacRae CA, Stricker BH, Hofman A, Uitterlinden AG, Levy D, Boerwinkle E, Metspalu A, Topol EJ, Chakravarti A, Gudnason V, Psaty BM, Roden DM, Meitinger T, Wichmann HE, Witteman JC*, Barnard J*, Arking DE* , Benjamin EJ*, Heckbert SR*, Kääb S*. Common variants in KCNN3 are associated with lone atrial fibrillation. Nat Genet. 2010 Mar;42(3):240-4. *These authors contributed equally to the work. Sotoodehnia N*, Isaacs A*, de Bakker PIW*, Dörr M*, Newton-Cheh C*, Nolte IM*, van der Harst P*, Müller M*, Eijgelsheim M*, Alonso A*, Hicks AA*, Padmanabhan S*, Hayward C*, Smith AV*, Polasek O*, Giovannone S*, Fu J*, Magnani JW, Marciante KD, Pfeufer A, Gharib SA, Teumer A, Li M, Bis JC, Rivadeneira F, Aspelund T, Köttgen A, Johnson T, Rice K, Sie MPS, Wang AY, Klopp N, Fuchsberger C, Wild SH, Leach IM, Estrada K, Völker U, Wright AF, Asselbergs FW, Qu J, Chakravarti A, Sinner MF, Kors JA, Petersmann A, Harris TB, Soliman EZ, Munroe PB, Psaty BM, Oostra BA, Cupples LA, Perz S, de Boer RA, Uitterlinden AG, Völzke H, Spector TD, Liu FY, Boerwinkle E, Dominiczak AF, Rotter JI, van Herpen G, Levy D, Wichmann HE, van Gilst WH, Witteman JCM, Kroemer HK, Kao WHL, Heckbert SR, Meitinger T, Hofman A, Campbell H, Folsom AR, van Veldhuisen DJ, Schwienbacher C, O'Donnell CJ, Volpato C, Caulfield MJ, Connell JM, Launer L, Lu X, Franke L, Fehrmann RSN, te Meerman G, Groen HJM, Weersma RK, van den Berg LH, Wijmenga C, Ophoff RA, Navis G, Rudan I*, Snieder H*, Wilson JF*, Pramstaller PP*, Siscovick DS*, Wang TJ*, Gudnason V*, van Duijn CM*, Felix SB*, Fishman GI * , Jamshidi Y*, Stricker BH*, Samani NJ*, Kääb S*, Arking DE*. Genetic variants in 22 loci are associated with cardiac ventricular conduction. Nat Genet . 2010 Dec;42(12):1068-76. PMID: 21076409; PMCID: PMC3338195. *These authors contributed equally to the work. Arking DE* , MJ Junttila*, P Goyette*, A Huertas-Vazquez*, M Eijgelsheim*, MT Blom*, C Newton-Cheh*, K Reinier, C Teodorescu, A Uy-Evanado, N Carter-Monroe, KS. Kaikkonen, ML Kortelainen, G Boucher, C Lagacé, A Moes, XQ Zhao, F Kolodgie, F Rivadeneira, A Hofman, JCM Witteman, AG Uitterlinden, RF Marsman, R Pazoki, A Bardai, RW Koster, A Dehghan, SJ Hwang, P Bhatnagar, W Post, G Hilton, RJ Prineas, M Li, A Köttgen, G Ehret, E Boerwinkle, J Coresh, WHL Kao, BM Psaty, GF Tomaselli, N Sotoodehnia, DS Siscovick, GL Burke, E Marbá¡n, PM Spooner, LA Cupples, J Jui, K Gunson, YA Kesäniemi, AAM Wilde, JC Tardif, CJ O'Donnell, CR Bezzina, R Virmani, BHCh Stricker*, HL Tan*, CM Albert*, A Chakravarti*, JD Rioux*, HV Huikuri*, SS Chugh*. Identification of a Sudden Cardiac Death Susceptibility Locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals. PLoS Genet. 2011 Jun;7(6):e1002158. Epub 2011 Jun 30. PMID: 21738491; PMCID: PMC3128111. *These authors contributed equally to the work. Huang H, Chanda P, Alonso A, Bader JS, Arking DE . Gene-based tests of association. PLoS Genet. 2011 Jul;7(7):e1002177. PMID: 21829371; PMCID: PMC3145613. Ellinor PT*, Lunetta KL*, Albert CM*, Glazer NL*, Ritchie MD*, Smith AV*, Arking DE * , Müller-Nurasyid M*, Krijthe BP*, Lubitz SA*, Bis JC*, Chung MK*, Dörr M*, Ozaki K*, Roberts JD, Smith JG, Pfeufer A, Sinner MF, Lohman K, Ding J, Smith NL, Smith JD, Rienstra M, Rice KM, Van Wagoner DR, Magnani JW, Wakili R, Clauss S, Rotter JI, Steinbeck G, Launer LJ, Davies RW, Borkovich M, Harris TB, Lin H, Völker U, Völzke H, Milan DJ, Hofman A, Boerwinkle E, Chen LY, Soliman EZ, Voight BF, Li G, Chakravarti A, Kubo M, Tedrow UB, Rose LM, Ridker PM, Conen D, Tsunoda T, Furukawa T, Sotoodehnia N, Xu S, Kamatani N, Levy D, Nakamura Y, Parvez B, Mahida S, Furie KL, Rosand J, Muhammad R, Psaty BM, Meitinger T, Perz S, Wichmann HE, Witteman JC, Kao WH, Kathiresan S, Roden DM, Uitterlinden AG, Rivadeneira F, McKnight B, Sjögren M, Newman AB, Liu Y, Gollob MH, Melander O, Tanaka T, Stricker BH, Felix SB, Alonso A, Darbar D, Barnard J, Chasman DI, Heckbert SR, Benjamin EJ, Gudnason V, Kääb S. Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nat Genet. 2012 Apr 29. doi: 10.1038/ng.2261. PMID: 22544366; PMCID: PMC3366038. *These authors contributed equally to the work. Chanda P, Yuhki N, Li M, Bader JS, Hartz A, Boerwinkle E, Kao WL, Arking DE . Comprehensive evaluation of imputation performance in African Americans. J Hum Genet. 2012 May 31. doi: 10.1038/jhg.2012.43. PMID: 22648186; PMCID: PMC3477509.