Transcript Genetics and Binge Eating: A Case

Genetics and Binge
Eating: A CaseControl Pilot Study
Tiffany Stewart, Ph.D.
Health Behavior
Pennington Biomedical Research Center
Specific Aims & Hypotheses
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Premise: Genes, behaviors, and the environment are intimately
related in the etiology and maintenance of obesity. Further, the
effects of the genotype can be amplified in an environment that
promotes obesity.
Primary Aim: To investigate the association between DNA sequence
variation in the genes of the leptin-melanocortin pathway and the
behavioral phenotype of binge eating.
Primary Hypothesis: The DNA sequence variation in the genes of
the leptin-melanocortin pathway is associated with a binge eating
phenotype, which may contribute to the development of obesity.
Secondary Aim: to implement methods to characterize a “pure”
binge eating phenotype.
Secondary Hypothesis: binge eating behavior is qualitatively
different from eating behavior in obese individuals without eating
disorders and nonobese individuals without eating disorders.
Principal Investigator: Tiffany M. Stewart, Ph.D.
Co-Investigators: Claude Bouchard, Ph.D., George Bray, M.D., Tuomo
Rankinen, Ph.D., Donna Ryan, M.D., & Don Williamson, Ph.D.
Significance
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Specific:
Genetic implications:
 Identification of genetic basis of hyperphagia in humans
 Reduction of heterogeneity of obesity
 Behavioral implications:
 Implications for diagnosis of binge eating (as well as other
eating disorders)
 Implications for phenotyping of binge eating
Overall:
 This study is designed to be the first in a series of studies to
investigate the relationship between genotypes and eating
behaviors in humans.
 This research may mark the beginnings of the attainment of
knowledge towards the development of treatment programs
and/or medications to be utilized in the future treatment of
binge eating and/or obesity. Ultimately, this information could
aid health care providers in the development of individualized
treatment and prevention programs for individuals
predisposed to weight gain or behaviors that may lead to
inappropriate weight gain.
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CNRU Project Summary
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Participants: Total (N=200)
 Cases (BED; N=100)
 Controls (non eating disorder; N=100)
 Men and Women ages 18-60, Weight range= normal to obese
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Matched experimental and control groups
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The present study hypothesizes behavioral phenotypes for genetic
association analysis based upon empirical classification data of eating
behavior.
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These behavioral phenotypes will be used to classify individuals.
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Genetic material, psychological assessment data, and body composition
data will be utilized for the analysis of the association between the
selected candidate genes and the behavioral phenotype, binge eating.
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This study will serve as a pilot study to begin recruitment and collect
preliminary data for an R21 application submitted to NIH.
Study Progress: Organization &
Training
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IRB approval
 The study was approved by the IRB.
Study Coordination
 Study coordination system in place.
Behavioral Phenotyping
 Formal training has been completed for members of the
psychological assessment team for the complex behavioral
phenotyping procedures, particularly with regard to the new
binge eating phenotyping, and reliability procedures on these
measurements are currently in progress.
 Reliability procedures underway. Progression of 99%
agreement between interviewers on measurement instruments
so far.
Genotyping
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Structure and procedures in place
Study Achievement: Behavioral
Phenotyping System
Problem:
Problematic Descriptions of
Binge Eating throughout
literature
Inconsistencies in
Psychological Diagnosis
Inconsistencies in Behavioral
Phenotyping in Genetic Studies
Controversial Outcomes
(Branson et al., 2003)
Solution:
Development of a finite
Behavioral Phenotyping
System
Study Achievement: Development of
Recruitment System
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An online recruitment system has been developed and beta tested. This
system is thought to overcome many of the obstacles of traditional
methods of recruiting and since this study relies on recruiting for its
success, it was necessary to develop for this project.
The PBRC online recruiting system employs an online and anonymous
forum by which individuals can provide PBRC with eating disorder
symptom information.
The online system notifies potential participants right away if they do not
meet criteria for the study. However, if a participant is a possible
candidate, based on the inclusion criteria, their information is securely
transported to a member of the psychology via electronic mail.
A member of the psychology team reviews the participant’s reported
symptoms and criteria and contacts the individual directly for their first
screening versus an individual with no prior knowledge of BED. This
allows for case sensitivity and the likelihood of weeding out non BED
cases in the early stages of the study so as to promote a more efficient
phenotyping system as well as more efficient study overall.
Online recruitment system beta test:
 7 days- approximately 55 individuals applied for the study via online
screening forms.
Traditional recruitment strategies (advertisements and phone calls) will be
utilized in conjunction with online strategies.
PBRC database as a source of recruitment
Study Progress: Scientific
Progress- R21 submission
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Principal Investigator: Tiffany Stewart, Ph.D.
Co-Investigators: Claude Bouchard, Ph.D., George Bray, M.D., Carlos Grilo,
Ph.D., Nathan Markward, Ph.D., Tuomo Rankinen, Ph.D., Donna Ryan,
M.D., and Donald Williamson, Ph.D.
The proposed pilot study is a collaborative effort between the Pennington
Biomedical Research Center and Yale University School of Medicine.
Application: 1 R21 DK07 4896-01
Submitted June 1, 2005
Center for Scientific Review Special Emphasis Panel (NIDDK)
Score 235
Overall review: The review viewed the application to have considerable
significance for the reduction of the heterogeneity in obesity research,
particularly in genetics. The investigative team was judged to have the
experience and expertise to successfully conduct the study. The research
environment was viewed as a supportive environment for the study.
Overall, the review posited that the strengths of the study outweighed the
weaknesses.
Received CNRU funding to begin recruiting participants and collecting
data
Resubmitted July 1, 2006
Study will include 600 participants (300 cases, 300 controls)
Study Progress: Scientific
Progress- R21 submission
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Key items addressed:
 Recruitment
 Since the submission of the initial proposal, PBRC has
added an online recruiting system, which has aided the
recruitment process tremendously for this study. We have
complete confidence in our recruitment abilities at PBRC for
this application.
 Genotyping
 Since the submission of the initial proposal, PBRC has
added a new genotype technology system, the Illumina.
With the Illumina system, we can increase genotyping
volume 10-fold without changing the budget.
Consequently, we can include additional candidate genes
from the same pathway.
 Addition of a statistical geneticist to team.
 To provide the expertise of statistical genetics of our
research team for the present project, we have added
Nathan Markward, Ph.D., M.P.H. to the research team to
meet this need.
Significance: CNRU
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CNRU Funding: “Headstart”- Key to Success of
project and program establishment
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Addressed R21 revisions: recruiting system
development, addition of personnel and coordination
team, staff training
Participant incentives
Behavioral phenotyping system development
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Utilization of behavioral core
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Collaboration with molecular genetics core
Summary & Future Directions
R21 submission June 1, 2005
 CNRU funding and study procedures
establishment
 R21 resubmission July 1, 2006
 Future Directions: R01
 Further establishment of Behavioral
Genetics Research Program
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Questions/Discussion