Ron Do, PhD
- ASSISTANT PROFESSOR | Genetics and Genomic Sciences
Research Topics:Cardiovascular, Computational Biology, Epigenetics, Genetics, Genomics, Human Genetics and Genetic Disorders, Systems Biology
Dr. Ron Do, Ph.D., is an Assistant Professor in the Department of Genetics and Genomic Sciences. He is appointed as a member of the Charles Bronfman Institute for Personalized Medicine, the Center for Statistical Genetics, the Icahn Institute for Genomics and Multiscale Biology, and the Zena and Michael A. Weiner Cardiovascular Institute.
Prior to joining Mount Sinai, Dr. Do was a Postdoctoral Fellow (2010 to 2013) and Instructor in Medicine (2013 to 2015) at the Center for Human Genetic Research at Massachusetts General Hospital and Harvard Medical School, and a research affiliate at the Broad Institute of MIT and Harvard.
Dr. Do is a human geneticist interested in understanding the genetic and biological bases of cardiovascular disease. He has pursued this interest by applying methods from human genetics, genetic epidemiology, statistical genetics, population genetics and computing to large-scale human genotyping and sequencing datasets. His research has focused on assessing the role of rare variants on myocardial infarction, inferring causal effects of risk factors for complex disease, and implementing a population genetics framework to measure differences in the efficiency of natural selection between human populations.
Multi-Disciplinary Training AreaGenetics and Genomic Sciences [GGS]
BSc, University of British Columbia
MSc, University of British Columbia
PhD, McGill University
Post-doc, Massachusetts General Hospital/Broad Institute/Harvard Medical School
Instructor, Harvard Medical School
Do Lab Description
The Do Lab's primary research aim is to discover the genetic and biological bases of cardiovascular disease. To this end, the Lab has focused on the following research areas.
1) Implementing computational approaches to analyze exome sequencing data with a view to discovering novel genes that confer risk for plasma lipids and myocardial infarction (MI). We led a study that analyzed exome sequencing data in families with Mendelian lipid disorders. In this project, we discovered compound heterozygote nonsense mutations in the ANGPTL3 gene as a cause of a novel Mendelian lipid disorder called Familial Combined Hypolipidemia (PMID: 20942659). We expanded upon this work to the study of a large-scale rare variant association study using exome sequencing in 10,000 cases and controls for MI.In this study, we identified a burden of rare mutations in the APOA5 and LDLR genes conferring risk for MI (PMID: 25487149). From this work, we have contributed insights and perspectives to the literature on how best to design and conduct rare variant association studies (PMID: 22983955).
2) Developing and implementing statistical approaches to analyze the causal effects of risk factors for complex disease. We have developed and implemented a method to isolate causal influences amongst a set of correlated risk factors for disease. We applied this approach to investigate the causal influence of plasma lipids on coronary artery disease (CAD). We discovered, using a model accounting for effects on low-density lipoprotein cholesterol and/or high-density lipoprotein cholesterol, that the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk, providing evidence that triglyceride-rich lipoproteins may be causally related to CAD (PMID: 24097064).
3) Developing and implementing a population genetics framework to measure the efficiency of natural selection in human populations with a view to understanding the genetic architecture of complex disease. We have developed a population genetics framework to assess the effect of a population bottleneck on the deleterious load in ancient and modern human populations. We observed no evidence of a difference in efficiency of natural selection between modern human populations. This work has improved our understanding of the role of specific population genetic forces in human history and their impact on the genetic architecture of complex disease (PMID: 25581429).
A complete list of publications from the Do lab can be found here.
Do R, Stitziel NO, Won HH, Jørgensen AB, Duga S, Angelica Merlini P, Kiezun A, Farrall M, Goel A, Zuk O, Guella I, Asselta R, Lange LA, Peloso GM, Auer PL, Girelli D, Martinelli N, Farlow DN, DePristo MA, Roberts R, Stewart AF, Saleheen D, Danesh J, Epstein SE, Sivapalaratnam S, Hovingh GK, Kastelein JJ, Samani NJ, Schunkert H, Erdmann J, Shah SH, Kraus WE, Davies R, Nikpay M, Johansen CT, Wang J, Hegele RA, Hechter E, Marz W, Kleber ME, Huang J, Johnson AD, Li M, Burke GL, Gross M, Liu Y, Assimes TL, Heiss G, Lange EM, Folsom AR, Taylor HA, Olivieri O, Hamsten A, Clarke R, Reilly DF, Yin W, Rivas MA, Donnelly P, Rossouw JE, Psaty BM, Herrington DM, Wilson JG, Rich SS, Bamshad MJ, Tracy RP, Cupples LA, Rader DJ, Reilly MP, Spertus JA, Cresci S, Hartiala J, Tang WH, Hazen SL, Allayee H, Reiner AP, Carlson CS, Kooperberg C, Jackson RD, Boerwinkle E, Lander ES, Schwartz SM, Siscovick DS, McPherson R, Tybjaerg-Hansen A, Abecasis GR, Watkins H, Nickerson DA, Ardissino D, Sunyaev SR, O'Donnell CJ, Altshuler D, Gabriel S, Kathiresan S. Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. Nature 2015 Feb; 518(7537).
Do R, Balick D, Li H, Adzhubei I, Sunyaev S, Reich D. No evidence that selection has been less effective at removing deleterious mutations in Europeans than in Africans. Nature genetics 2015 Feb; 47(2).
Do R, Willer CJ, Schmidt EM, Sengupta S, Gao C, Peloso GM, Gustafsson S, Kanoni S, Ganna A, Chen J, Buchkovich ML, Mora S, Beckmann JS, Bragg-Gresham JL, Chang HY, Demirkan A, Den Hertog HM, Donnelly LA, Ehret GB, Esko T, Feitosa MF, Ferreira T, Fischer K, Fontanillas P, Fraser RM, Freitag DF, Gurdasani D, Heikkilä K, Hyppönen E, Isaacs A, Jackson AU, Johansson A, Johnson T, Kaakinen M, Kettunen J, Kleber ME, Li X, Luan J, Lyytikäinen LP, Magnusson PK, Mangino M, Mihailov E, Montasser ME, Müller-Nurasyid M, Nolte IM, O'Connell JR, Palmer CD, Perola M, Petersen AK, Sanna S, Saxena R, Service SK, Shah S, Shungin D, Sidore C, Song C, Strawbridge RJ, Surakka I, Tanaka T, Teslovich TM, Thorleifsson G, Van den Herik EG, Voight BF, Volcik KA, Waite LL, Wong A, Wu Y, Zhang W, Absher D, Asiki G, Barroso I, Been LF, Bolton JL, Bonnycastle LL, Brambilla P, Burnett MS, Cesana G, Dimitriou M, Doney AS, Döring A, Elliott P, Epstein SE, Eyjolfsson GI, Gigante B, Goodarzi MO, Grallert H, Gravito ML, Groves CJ, Hallmans G, Hartikainen AL, Hayward C, Hernandez D, Hicks AA, Holm H, Hung YJ, Illig T, Jones MR, Kaleebu P, Kastelein JJ, Khaw KT, Kim E, Klopp N, Komulainen P, Kumari M, Langenberg C, Lehtimäki T, Lin SY, Lindström J, Loos RJ, Mach F, McArdle WL, Meisinger C, Mitchell BD, Müller G, Nagaraja R, Narisu N, Nieminen TV, Nsubuga RN, Olafsson I, Ong KK, Palotie A, Papamarkou T, Pomilla C, Pouta A, Rader DJ, Reilly MP, Ridker PM, Rivadeneira F, Rudan I, Ruokonen A, Samani N, Scharnagl H, Seeley J, Silander K, Stančáková A, Stirrups K, Swift AJ, Tiret L, Uitterlinden AG, van Pelt LJ, Vedantam S, Wainwright N, Wijmenga C, Wild SH, Willemsen G, Wilsgaard T, Wilson JF, Young EH, Zhao JH, Adair LS, Arveiler D, Assimes TL, Bandinelli S, Bennett F, Bochud M, Boehm BO, Boomsma DI, Borecki IB, Bornstein SR, Bovet P, Burnier M, Campbell H, Chakravarti A, Chambers JC, Chen YD, Collins FS, Cooper RS, Danesh J, Dedoussis G, de Faire U, Feranil AB, Ferrières J, Ferrucci L, Freimer NB, Gieger C, Groop LC, Gudnason V, Gyllensten U, Hamsten A, Harris TB, Hingorani A, Hirschhorn JN, Hofman A, Hovingh GK, Hsiung CA, Humphries SE, Hunt SC, Hveem K, Iribarren C, Järvelin MR, Jula A, Kähönen M, Kaprio J, Kesäniemi A, Kivimaki M, Kooner JS, Koudstaal PJ, Krauss RM, Kuh D, Kuusisto J, Kyvik KO, Laakso M, Lakka TA, Lind L, Lindgren CM, Martin NG, März W, McCarthy MI, McKenzie CA, Meneton P, Metspalu A, Moilanen L, Morris AD, Munroe PB, Njølstad I, Pedersen NL, Power C, Pramstaller PP, Price JF, Psaty BM, Quertermous T, Rauramaa R, Saleheen D, Salomaa V, Sanghera DK, Saramies J, Schwarz PE, Sheu WH, Shuldiner AR, Siegbahn A, Spector TD, Stefansson K, Strachan DP, Tayo BO, Tremoli E, Tuomilehto J, Uusitupa M, van Duijn CM, Vollenweider P, Wallentin L, Wareham NJ, Whitfield JB, Wolffenbuttel BH, Altshuler D, Ordovas JM, Boerwinkle E, Palmer CN, Thorsteinsdottir U, Chasman DI, Rotter JI, Franks PW, Ripatti S, Cupples LA, Sandhu MS, Rich SS, Boehnke M, Deloukas P, Mohlke KL, Ingelsson E, Abecasis GR, Daly MJ, Neale BM, Kathiresan S. Common variants associated with plasma triglycerides and risk for coronary artery disease. Nature genetics 2013 Nov; 45(11).
Do R, Kathiresan S, Abecasis GR. Exome sequencing and complex disease: practical aspects of rare variant association studies. Human molecular genetics 2012 Oct; 21(R1).
Musunuru K, Pirruccello JP, Do R, Peloso GM, Guiducci C, Sougnez C, Garimella KV, Fisher S, Abreu J, Barry AJ, Fennell T, Banks E, Ambrogio L, Cibulskis K, Kernytsky A, Gonzalez E, Rudzicz N, Engert JC, DePristo MA, Daly MJ, Cohen JC, Hobbs HH, Altshuler D, Schonfeld G, Gabriel SB, Yue P, Kathiresan S. Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia. The New England journal of medicine 2010 Dec; 363(23).