What drew you to epidemiology?
In answering this question, I like to recount the story of
the Broad Street pump. In 1850, people in London were
dying of diarrheal illness at an alarming rate. Dr. John Snow
used the basic tenant of epidemiology—
the analysis of candidate exposures in
relation to a disease—to address this dire
situation. He concluded that a particular
water pump harbored an agent that contributed
to this illness and recommended
that the pump be shut down. Municipal
authorities reluctantly heeded his advice,
and deaths from cholera decreased
markedly.
This story illustrates the power of epidemiology to shed light on disease processes, even when the science to completely understand them is not yet developed. In this instance, not only was the identity of cholera unknown, the entire field of bacteriology was in its infancy. Today, as I work at the Channing Lab in Boston with colleagues such as Jae Hee Kang, ScD, the array of exposures we can assess in relation to glaucoma is quite sophisticated. They include serum and DNA biomarkers, dietary data, anthropometric factors, and other lifestyle attributes. I therefore feel that epidemiology has the potential to unlock clues about diseases like primary open-angle glaucoma (POAG) and exfoliation glaucoma. Of course, other scientific disciplines will be needed to augment knowledge gained from epidemiology in order to develop a complete picture of these conditions.
What has your study of diabetes revealed thus far
about glaucoma, and what is the next question in this
area you hope to examine?
Our work and the work of others point to a modest
positive relation between type 2 diabetes mellitus (T2D)
and POAG. Conversely, there is not a single adequately
powered study to show a significant inverse relation
between T2D and POAG. Our work specifically indicates
that something about insulin resistance, independent of
body mass index, contributes to POAG.1 It is exciting that
a high-throughput genotyping effort performed by researchers
from the Rotterdam Study revealed that genetic
variants in the CDKN2B gene are linked to variance in cupto-
disc ratio.2 CDKN2B gene variants are also linked to
T2D.3 In conjunction with Janey Wiggs, MD, PhD, we just completed a study showing that CDKN2B gene variants
are also related to POAG, and those results will be published
in the near future. What seems to be emerging is
that POAG and insulin resistance may share some genetic
biomarkers. In the future, we hope to find
gene-environment interactions focused on
insulin resistance in relation to POAG.
Where does the NIH-funded Genomewide
Association Study stand? What
do you hope to learn from this effort?
We completed a genome-wide association
study of 1,000 POAG cases and
1,182 controls as part of the Glaucoma
Genes and Environment (GLAUGEN)
Initiative supported by the National
Human Genome Research Institute. The
data on genotype and phenotype were posted on dbGap
on December 21, 2010.4 The scientific community can apply
to the Data Access Committee at the NIH to review the
data, although there is a 1-year embargo on publications
related to these data by outside investigators. The completion
of this study is only one in a series of efforts to discover
how genes, gene-gene interactions, and gene-environment interactions contribute to POAG. Another large consortium, the
National Eye Institute Glaucoma Human Genetics Collaboration
(NEIGHBOR), under the direction of Dr. Wiggs at Harvard and
Michael Hauser, PhD, at Duke University in North Carolina, will
also contribute cases and controls to further this cause. The genotypes
for 5,118 total participants in NEIGHBOR were ready for
data cleaning as of January 10, 2011.
We have already gained insight into the genetic architecture of POAG from the work completed thus far. We know that no common genetic loci of major effect are operative in this disease. We also know that the genetic architecture of POAG is sufficiently complex that we will need to combine data from GLAUGEN, NEIGHBOR, and possibly other consortia in order to confidently identify genetic loci associated with this disease. We hope this work will completely redefine POAG, a condition that is essentially a diagnosis of exclusion, into a group of disorders with discrete biochemical abnormalities. Furthermore, we hope that targeting these novel biochemical targets will lead to more cost-effective measures to preserve the vision of patients with POAG.
How do you juggle your roles as educator, scientist, and
physician?
This is easy. I treat my clinic like my laboratory, I conduct my
teaching assignments like research projects, and I view my research
as an opportunity to develop better strategies with which to care
for patients. In other words, all of these roles are interrelated.
How does a New Yorker survive in Red Sox Nation, and
what prompted your plan to run in the Boston Marathon?
One time, I was taking the train to the Red Sox–New York
Yankees game at Fenway Park while wearing a Yankees shirt. Five
burly gentlemen began to descend upon me. I looked up and said,
“Take it easy, guys. I don't work for a terrorist organization.” They
laughed and walked away. You cannot take New York out of a
New Yorker, but with disarming wit and respect, it is quite easy to
survive in Red Sox Nation. You just cannot take yourself too seriously.
Plus, I have to admit the Red Sox are pretty good.
I am running the Boston Marathon to raise awareness about glaucoma and to raise money for glaucoma research. I have networked with my fellow runners and adhere to a schedule of training sessions designed by the Fitcorp training group. I treat this schedule like a series of homework assignments or work deadlines and try to stick with it. In fact, it is time to go running.
