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Braxton D. Mitchell, PhD, MPH

Academic Title:

Professor

Primary Appointment:

Medicine

Secondary Appointment(s):

Epidemiology & Public Health

Additional Title:

Vice Chair for Research, Division of Endocrinology, Diabetes & Nutrition, Dept. of Medicine

Location:

HSF III, 670 West Baltimore Street, Room 4108C

Phone (Primary):

(410) 706-0161

Education and Training

Princeton University, B.A, Psychology, 1978

University of Michigan, M.P.H., Epidemiology, 1982

University of Michigan, Ph.D, Epidemiology, 1987

University of Texas Health Science Center, Postdoctoral, Epidemiology, 1991

 

Biosketch

Dr. Mitchell is a genetic epidemiologist who has studied the genetics of complex diseases for many years. He has directed and played leading roles in numerous studies of cardiometabolic and bone health, whose goals have been to uncover the genetic architecture of these traits, identify genetic variants affecting disease risk, and to determine how the effects of these variants are modified by lifestyle risk factors. His research has been continuously funded by the NIH for over 25 years. His current research focuses on type 2 diabetes mellitus, cardiovascular disease, ischemic stroke, osteoporosis, osteoarthritis, and obesity. Dr. Mitchell has been a core investigator in the Amish Complex Disease Genetics program for the past 15 years, where he has led or participated in numerous discoveries of rare large effect variants that are enriched in this founder population. Current efforts in this study involve integration of whole genome and exome sequencing and other –omics data. He has published over 400 papers from his research.

Dr. Mitchell has served in multiple leadership positions in large consortia and on multiple editorial boards. He serves as the Associate Director of both the Mid-Atlantic Nutrition Obesity Research Center (NORC) and the Baltimore Diabetes Research Center (DRC). For these centers he directs a genomics core whose role is to provide support to investigators in their diabetes, obesity, and nutrition-related research.  He has played an active role in the graduate program throughout his tenure at Maryland, including directing the Human Genetics Program for eight years.  Throughout his career, he has mentored a large number of talented students, fellows, and junior faculty to pursue academic careers in translational research.

Research/Clinical Keywords

genetic epidemiology, diabetes, cardiovascular disease, Amish, genetics

Highlighted Publications

Mitchell BD, Lee W-J, Tolea MI, Shields K, Ashktorab Z, Magder LS, Ryan KA, Pollin TI, McArdle PF, Shuldiner AR, Schäffer AA.  Living the good life?  Mortality patterns and hospital utilization in the Lancaster County Amish.  PLoS ONE 7(12):e51560, 2012.  PMC3526600.

Shen H, Damcott CM, Rampersaud E, Pollin TI, Horenstein R, McArdle PF, Peyser PA, O’Connell JR, Bielak  LF, Post W, Chang Y-P C, Ryan KA, Miller M, Shelton J, Shuldiner AR, Mitchell BD.  Familial defective apolipoprotein B-100 and increased low-density lipoprotein cholesterol and coronary artery calcification in the Old Order Amish.  Arch Intern Med 170:1850-1855, 2010.  PMC3587042.

Rampersaud E, Mitchell BD, Pollin TI, Fu M, Shen H, O’Connell JR, Ducharme JL, Hines S, Sack P, Naglieri R, Shuldiner AR, Snitker S.  Physical activity and the association of common FTO gene variants with body mass index and obesity.  Arch Intern Med 168(16):1791-1797, 2008. PMC3635949.

Pulit S, McArdle PF, Wong Q, Malik R, Gwinn K, . . . , Mitchell BD*, Rosand J*.  Loci associated with ischaemic stroke and its subtypes (SiGN): a genome-wide association study.  Lancet Neurol 15:174-184, 2016. PMC4912948.

http://www.ncbi.nlm.nih.gov/sites/myncbi/braxton.mitchell.1/collections/50650637/public/

 

Additional Publication Citations

MacClellan LR, Mitchell BD, Cole JW, Wozniak MA, Stern BJ, Giles WH, Brown DW, Sparks MJ, Kittner SJ, for the Stroke Prevention in Young Women Study Group.  Familial aggregation of ischemic stroke in young women: The Stroke Prevention in Young Women Study.  Genet Epidemiol 30:602-608, 2006.PMID16868965.

Mitchell BD, McArdle PF, Shen H, RampersaudE, PollinTI, Bielak LF, Jaquish C, Douglas JA, Roy-Gagnon M-H, Sack P, Naglieri R, Hines S, Horenstein RB, Chang Y-P C, Post W, Ryan KA, Brereton NH, Pakyz RE, Sorkin J, Damcott CM, O’Connell JR, Mangano C, Corretti M, Vogel R, Herzog W, Weir MR, Peyser PA, Shuldiner AR.  The genetic response to short-term interventions affecting cardiovascular function:  rationale and design of the HAPI Heart Study.  Am Heart Journal 155:823-828, 2008. PMC2443415.

Horenstein RB, Mitchell BD, Post WS, Leutjohann D, von Bergmann K, Ryan KA, Terrin M, Shuldiner AR, Steinle NI. The ABCG8 G574R variant, serum plant sterol levels, and cardiovascular disease risk in the Old Order Amish.  Arterioscl Thromb Vasc Biol 33:413-9, 2013. PMC3817740.

Yerges-Armstrong LM, Shen H, Streeten EA, Shuldiner AR, Mitchell BD.  Decreased bone mineral density in subjects carrying familial defective Apolipoprotein B-100.  (2013). J Clin Endocrinol Metab 12:E1999-2005.  PMC3849668.

Seifter A, Singh S, McArdle PF, Ryan KA, Shuldiner AR, Mitchell BD, Schäffer AA. Analysis of the bereavement effect after the death of a spouse in the Amish. BMJ Open 4(1): e003670, 2014. PMC3902313.

Yerges-Armstrong L, Yau MS, Liu Y, Krishnan S, Renner JB, Eaton CB, Kwoh CK, Nevitt MC, Duggan DJ, Mitchell BD, Jordan JM, Hochberg MC, Jackson RD. Association analysis of BMD-associated SNPs with knee osteoarthritis.  J Bone Miner Res 29(6):1373-79, 2014. PMC4080308.

Mitchell BD, Fornage M, McArdle PF, Cheng YC, Pulit SL, . . ., de Bakker PIW, on behalf of the Stroke Genetics Network (SiGN). Using previously genotyped controls in genome-wide association studies (GWAS): application to the Stroke Genetics Network (SiGN). Front Genet 5:95, 2014. PMC4010766.

Mitchell AB, Cole JW, McArdle PF, Cheng Y-C, Ryan KA, Sparks MJ, Mitchell BD, Kittner SJ.  Obesity increases risk of ischemic stroke in young adults.  Stroke 46(6):1690-92, 2015.  PMC4458137.

Cheng YC, Stanne TM, Giese AK, …, Mitchell BD.  Genome-wide association analysis of young onset stroke identifies a locus on 10q25 near HABP2.  Stroke 47:307-16, 2016. PMC4729659.

Research Interests

There is a substantial genetic contribution for susceptibility to most common diseases and traits, although for many of these diseases, specific DNA polymorphisms related to disease susceptibility have yet to be identified. My research program utilizes a variety of approaches to try to dissect the genetic and environmental determinants of a variety of complex diseases, including type 2 diabetes, cardiovascular disease, stroke, hypertension, osteoporosis and obesity. The goal of these efforts is to detect and identify common gene variants that may influence susceptibility to one or more of these disorders, and to determine how these variants may interact with other gene variants and/or with lifestyle factors to influence disease risk.

Much of my research is carried out in large population studies and includes collaborations with clinicians, molecular biologists, and geneticists.  My current research is focused mainly in the areas of cardiometabolic health, stroke, and osteoarthritis.  In addition to my work with the Old Order Amish community, my major research projects include the genetics of ischemic stroke in the Stroke Genetics Network, and the genetics of osteoarthritis in the Osteoarthritis Initiative.

Awards and Affiliations

Klare Memorial Scholarship (University of Michigan), 1982.

Diabetes Epidemiology Training Grant (University of Michigan), 1984-87.

Modan Award for top scoring epidemiology abstract submitted to the Ann Scientific Mtg of the American Diabetes Assoc.  (with Kao WHL), 2000.

Faculty Mentor Award. Program in Epidemiology and Human Genetics, University of Maryland School of Medicine, 2006.  

Harry and Jeanette Weinberg Foundation Research Award for American Heart Association Grant-in-Aid, 2008.

Faculty Mentor Award. Program in Epidemiology and Human Genetics, University of Maryland School of Medicine, 2011.

Outstanding Alumnus Award.  St. Paul’s School.  Brooklandville, MD, 2011.

Research Faculty Teacher of the Year Award.  Div of Endocrinol, Diabetes, & Nutr. Dept of Medicine, Univ of Maryland School of Medicine, 2012.

Chairman’s Special Achievement Award, Dept. of Medicine, Dept of Medicine, University of Maryland School of Medicine, 2016.

 

Grants and Contracts

Active

 

NIH                                                         (Hong/Mitchell)          9/10/2015-6/30/2020                             0.6    cal. months

U01MH1D8148                                                                     $3,180,400

Amish Connectome Project on Mental Illness

The Amish Connectome Project will collect data from large, multi-generational Old Order Amish families with a high prevalence of mental disorders. The project aims to extend the ongoing Human Connectome Project with state of the art cerebral connectomics

Role:   PI

 

NINDS                                                   (Kittner/Mitchell)         1/15/2018-12/31/22                               1.8    cal. months

R01NS105150-01                                                                 $408,027

Genetics of Early-Onset Ischemic Stroke Consortium

The goals of this project are to study the early-onset stroke has a higher heritability than older- onset stroke, and GWAS based on early-onset stroke cases only or using age-informed analysis models have uncovered new stroke-associated variants.

Role:   PI

 

NINDS                                                   (Mitchell)                   6/1/2017-2/28/22                                   1.8    cal. months

R01NS100178-01A1                                                            $452,055

Genetics of ischemic stroke in the SiGN Consortium

The goals of this application are to determine the genetic determinants of stroke in the Stroke Genetics Network (SiGN), including an analysis of rare variants associated with stroke subtypes, and to make the SiGN resource accessible to the stroke genetics community.

Role:   PI

 

NIDDK                                                   (Taylor & Mitchell)       9/15/2005-8/31/20                                 1.3    cal. months

5P30DK072488-13                                                               $819,118

Mid-Atlantic Nutrition Obesity Research Center

The NORC will focus on the influence of nutrition and exercise on risk for age-related chronic diseases, including obesity, type 2 diabetes, hypertension, cardiovascular disease (CVD), sleep disordered breathing, and osteoporosis.

Role:   PI

 

General Hospital Corp. d/b/a                 (Mitchell)                   7/1/2015-4/30/20                                   0.5    cal. months

Massachusetts General

Hospital

 

R01NS086905                                                                      $117,739

MRI-GENetics Interface Exploration (MRI-GENIE) Study

The goal of this study is to develop and validate automated methods for extracting brain lesion phenotypes from MRI data and then applying these methods to MRIs collected from subjects in the SiGN Neuroimaging Repository to examine their association with

Role:   Subcontract PI

Regeneron Pharmaceuticals,                (Mitchell & Pollin)        4/24/2015-4/23/20                                 1.1    cal. months

Inc

 

N/A                                                                                        $790,257

Regeneron Research collaboration Agreement

This project is to obtain whole exome sequencing in the Amish and identify large effect variants segregating in the Amish.

Role:   PI

 

NIBIB                                                                                    8/1/2012-7/31/20                                   0.4    cal. months

EB015611-05                                                                        $304,348

SOLAR-Eclipse computational tools for imaging genetics

The goal of this study is to develop tools and computational methods for integrating and analyzing multidimensional imaging data in genetic studies.

Role:   Co-Investigator

 

NHLBI                                                    (Lewis)                     7/1/2017-6/30/22                                   0.6    cal. months

HL137922-01                                                                        $250,000

The Impact of Carboxylesterase 1 (CES1) in personalized antiplatelet therapy

This study prospectively assesses the impact of genetic variation in the carboxylesterase 1 (CES1) gene on platelet aggregation in response to the P2Y12 receptor inhibitors clopidogrel

and ticagrelor.

Role:   Co-Investigator

 

Fred Hutchinson Cancer                       (Reiner)                    8/30/2015-3/31/21                                 0.1    cal. months

Research Center

R01 HL136574                                                                      $25,157

Whole Genome Sequence Analysis of Ischemic Stroke in the Women's Health Initiative

The objective of this study is to identify rare variants associated with ischemic stroke and its subtypes in the WHI, replicate observed associations in the SiGN Consortium, and assess the biological mechanisms of

underlying observed variants via analysis

Role:   Co-Investigator

Community Service

Student Support Netwoirk, Board of Directors, 2018-

Professional Activity

Steering Committee, International Type 2 Diabetes Linkage Analysis Consortium, 1998-2004

Steering Committee, IRAS Family Study, 1999-2004

Scientific Sessions Planning Committee, American Diabetes Association, 2001-2002

NIH Study Section standing member, Cardiovascular and Sleep Epidemiology Study Section [CASE], 2002-2006

Co-Editor, Diabetes/Metabolism Research and Reviews, 2002-2014 

Associate Editor, Diabetes, 2009-2016

Editorial Advisory Board, Diabetes Management, 2011-2014

Faculty mentor, Young Investigator Initiative (YII) grant writing program, United States Bone and Joint Decade, 2011-present

Steering Committee, Stroke Genetics Network (SiGN), 2012-present

NIH Study Section Standing member, Kidney, Obesity, Nutrition, and Diabetes Study Section [KNOD], 2013-2017

External Scientific Review Board, Cardiac Health Project (ICHP), Walter Reed National Military Medical Center, Bethesda, MD, 2013-present

Center for Inherited Disease Research (CIDR) Access Committee, NHGRI, 2014-2018

 

Links of Interest

Previous Positions

  • 1991-1994: Assistant Professor, Department of Medicine, Division of Clinical Epidemiology, University of Texas Health Science Center, San Antonio, Texas
  • 1994-2000: Staff Scientist (1994-96), Associate Scientist (1996-98), Scientist (1999-2000), Southwest Foundation for Biomedical Research, San Antonio, TX