News and Announcements from Biomedical Genetics

 March 7, 2014


Dr. Lindsay Farrer, Professor and Chief of the Biomedical Genetics division and Director of TTPAS, and his colleagues reported in several recently published papers the discovery of multiple genes associated with risk of addiction to cocaine, opioids, and alcohol. Although it has been recognized for several decades that there is a strong heritable component of addiction to many drugs, robust evidence for contribution of specific genes has been meager, especially for dependence on cocaine or opioids.

Dr. Farrer has been studying genetic factors predisposing to substance dependence for more than 15 years in collaboration with other researchers at Yale University and the University of Pennsylvania. African American (AA) and European American (EA) families and unrelated individuals (> 10,000 individuals in total) were recruited and screened for numerous substance dependence diagnoses, including opioids, cocaine, alcohol, and nicotine. Recently, Dr. Farrer and Dr. Richard Sherva, a BUSM faculty member in the Biomedical Genetics division, directed genome-wide association analyses using detailed standardized psychiatric interview and demographic data, and genotypes for several million single nucleotide polymorphisms (SNPs) obtained from approximately 5,700 study participants.

In the study focused on opioid dependence, published in Biological Psychiatry (, genome-wide significant evidence of association was identified in the AA group with a SNP in the KCNG2 gene which encodes a neuronal voltage gated potassium channel (figure 1).

Figure 1: Association results from the KCNG2 gene on chromosome 18 with opioid dependence
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Several genes with the strongest evidence for association are clustered in biological pathways involved in the regulation of calcium and potassium levels and synaptic long term potentiation in neurons (figure 2).

Figure 2: The role of genes identified in GWAS of AA subjects in the canonical pathway “synaptic long term potentiation.”

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In a separate paper published in Molecular Psychiatry (, the investigative team reported a genome-wide significant association between risk for cocaine dependence and a SNP in FAM53B, a gene involved in regulating cell proliferation (figure 3).

Figure 3: Association results from the FAM53B gene on chromosome 10 with cocaine dependence.

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This finding was evident in both AA and EA samples. Intriguingly, several of the most significantly associated genes cluster in pathways related to calcium/potassium signaling.

Most recently, Dr. Farrer, Dr. Sherva and their collaborators, identified association of alcohol dependence with several previously reported mutations in alcohol metabolizing enzymes. Importantly, the most significant findings were observed with two distinct non-synonymous (.i.e., predicted to be functionally relevant) mutations in the alcohol dehydrogenase 1B gene (ADH1B) that are population-specific (figures 4 and 5).

Figure 4: Association results within the alcohol metabolizing gene cluster on chromosome 4 in AAs

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Figure 5: Association results within the alcohol metabolizing gene cluster on chromosome 4 in EAs

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Novel associations were also identified in one small intergenic region on chromosome 2 in both the EA and AA cohorts, and population-specific significant associations were identified with markers located on chromosomes 5, 9 and 19. These findings were also published in Molecular Psychiatry (

These results reveal several interesting facts about addiction. First, certain risk variants are population-specific while others are shared among individuals of AA and EA ancestry. Second, the genetic susceptibility to substance dependence is likely mediated by proteins involved in both the metabolism of substances as well as those involved in brain development, learning, and neuronal excitability. Finally, some genes appear to alter an individual’s risk for dependence on a specific substance, while others act as determinants of general substance dependence susceptibility.   


October 27, 2013

Eleven New Genetic Susceptibility Factors for Alzheimer’s Disease Discovered Through the Largest Study
Lindsay Farrer
, chief of Biomedical Genetics at Boston University School of Medicine, is interviewed on exciting new Alzheimer Research results from the International Genomics Alzheimer’s Project in an article by Science Daily.

September 10, 2013

Boston Babies to Have DNA Sequenced in Genome Study
(Boston) – Lindsay Farrer, chief of Biomedical Genetics at Boston University School of Medicine, was highlighted in an article by The Daily Free Press about a study that will have the DNA of many Boston babies sequenced. Dr.Farrer gives his insight about the five-year study that will explore the effect of DNA sequencing on the future medical care of Boston newborns.

July 2013

Genomic Studies of Non-Caucasians Could Deepen Understanding of Alzheimer’s Disease
(Boston)    Neurology Reviews interviews Lindsay Farrer, chief of Biomedical Genetics at Boston University School of Medicine,  regarding his presentation on Alzheimer Research of non-Caucasions at the  Alzheimer’s Association International Conference 2013.

Spring 2013

Biomedical Genetics in Spring 2013 BUMC Campus Alumni News
Boston) – Four researchers and one educator from the BUMC Biomedical Genetics section were highlighted in the Spring 2013 edition of the Boston University School of Medicine Campus Alumni News.

Shoumita Dasgupta, Ph.D., is quoted in a section of the front page article, Creating Dr.Right, describing the interdisciplinary training of next generation biomedical scientists.

According to the article covering the $2.5 Million Addiction Training Grant Awarded by Burroughs Wellcome Fund, Lindsay Farrer, Ph.D., and Timothy Heeren, Ph.D., professor of biostatistics at Boston University School of Public Health (BUSPH), will lead the Transformative Training Program in Addiction Science (TTPAS).

Clinton Baldwin, Ph.D., and Mark Logue, Ph.D., are co-first authors of a paper detailing the findings of a newly identified gene linked to PTSD.

Gyungah Jun, Ph.D., was mentioned as the lead author for a paper about the study that identified a gene linking cataracts and Alzheimer’s disease.

March 3, 2013

International consortium discovers seven new genomic regions associated with age-related macular degeneration
(Boston) – An international group of researchers has discovered seven new regions of the human genome—called loci—that are associated with increased risk of age-related macular degeneration (AMD), a leading cause of blindness. The AMD Gene Consortium, a network of international investigators representing 18 research groups, also confirmed 12 loci identified in previous studies. The study, which is published online in Nature Genetics and represents the most comprehensive genome-wide analysis of genetic variations associated with AMD, was supported by the National Eye Institute (NEI), a part of the National Institutes of Health.

Lindsay A. Farrer, PhD, chief of the biomedical genetics section and professor at Boston University Schools of Medicine (BUSM) and Public Health (BUSPH), is co-lead author of the study.

“This compelling analysis by the AMD Gene Consortium demonstrates the enormous value of effective collaboration,” said NEI Director Paul A. Sieving, MD, PhD. “Combining data from multiple studies, this international effort provides insight into the molecular basis of AMD, which will help researchers search for causes of the disease and will inform future development of new diagnostic and treatment strategies.”

Since the 2005 discovery that certain variations in the gene for complement factor H—a component of the immune system—are associated with major risk for AMD, research groups around the world have conducted genome-wide association studies to identify other loci that affect AMD risk. These studies were made possible by tools developed through the Human Genome Project, which mapped human genes, and related projects, such the International HapMap Project, which identified common patterns of genetic variation within the human genome.

The AMD Gene Consortium combined data from 18 research groups to increase the power of prior analyses. The current analysis identified seven new loci near genes. As with the previously discovered 12 loci, these seven loci are scattered throughout the genome on many different chromosomes.

“A large number of samples was needed to detect additional genetic variants that have small but significant influences on a person’s disease risk,” said Hemin Chin, PhD, NEI associate director for ophthalmic genetics, who assembled the consortium and helped coordinate the study. “By cataloging genetic variations associated with AMD, scientists are better equipped to target corresponding biological pathways and study how they might interact and change with age or other factors, such as smoking.”

The consortium’s analysis included data from more than 17,100 people with the most advanced and severe forms of AMD, which were compared to data from more than 60,000 people without AMD. The 19 loci that were found to be associated with AMD implicate a variety of biological functions, including regulation of the immune system, maintenance of cellular structure, growth and permeability of blood vessels, lipid metabolism and atherosclerosis.

As with other common diseases, such as type 2 diabetes, an individual person’s risk for getting AMD is likely determined not by one but many genes. Further comprehensive DNA analysis of the areas around the 19 loci identified by the AMD Gene Consortium could turn up undiscovered rare genetic variants with a disproportionately large effect on AMD risk. Discovery of such genes could greatly advance scientists’ understanding of AMD pathogenesis and their quest for more effective treatments.

AMD affects the macula, a region of the retina responsible for central vision. The retina is the layer of light-sensitive tissue in the back of the eye that houses rod and cone photoreceptor cells. Compared with the rest of the retina, the macula is especially dense with cone photoreceptors and is what humans rely on for tasks that require sharp vision, such as reading, driving and recognizing faces. As AMD progresses, such tasks become more difficult and eventually impossible. Some kinds of AMD are treatable if detected early, but no cure exists. An estimated 2 million Americans have AMD.

Scientists have shown that age, diet, and smoking influence a person’s risk of developing AMD. Genetics also plays a strong role. AMD often runs in families and is more common among certain ethnicities, such as Asians and people of European descent.  AMD typically presents later in life, but identifying genetic variants associated with the disease, all of which are present at birth, could help future studies determine how to stop the disease from progressing and even from occurring.

“Genetic research allows us to piece together disease pathways that may have their starting point much earlier in life,” said Farrer. “These newly identified genes, individually and collectively, provide novel clues and targets to evaluate for their potential therapeutic benefits.”

For more information about AMD, visit

Goncalo Abecasis, DPhil, from the University of Michigan; Iris Heid, PhD, from the University of Regensburg, Germany; and Jonathan L. Haines, PhD, from Vanderbilt University are the study’s other co-lead authors. Funding for the research conducted at BUSM for this study was provided in part by the National Institutes of Health under grant award number R01-EY014458 and the Edward N. & Della L. Thome Memorial Foundation.

March 2011

Alzheimer’s Disease Consortium Identifies Four New Genes For Alzheimer’s Disease Risk

In the largest study of its kind, researchers from a consortium led by the University of Pennsylvania School of Medicine, Boston University School of Medicine and the University of Miami identified four new genes linked to Alzheimer’s disease. Each gene individually adds to the risk of having this common form of dementia later in life. These new genes offer a portal into what causes Alzheimer’s disease and is a major advance in the field.

The study, conducted by the Alzheimer’s Disease Genetics Consortium, reports genetic analysis of more than 11,000 people with Alzheimer’s disease and a nearly equal number of elderly people who have no symptoms of dementia. Three other consortia contributed confirming data from additional people, bringing the total number of people analyzed to over 54,000. The consortium also contributed to the identification of a fifth gene reported by other groups of investigators from the United States, the United Kingdom, France and other European countries.  The findings appear in the current issue of Nature Genetics.

The study is the result of a large collaborative effort with investigators from 44 universities and research institutions in the United States, led by Gerard D. Schellenberg, PhD, at Penn, with primary analysis sites at Boston, led by Lindsay A. Farrer, PhD, and Miami, led by Margaret A. Pericak-Vance, PhD.

“This is the culmination of years of work on Alzheimer’s disease by a large number of scientists, yet it is just the beginning in defining how genes influence memory and intellectual function as we age. We are all tremendously excited by our progress so far, but much remains to be done, both in understanding the genetics and in defining how these genes influence the disease process,” Schellenberg said.

Until recently, only four genes associated with late-onset Alzheimer’s have been confirmed, with the gene for apolipoprotein E-e4, APOE-e4, having the largest effect on risk. The Nature Genetics studies add another four — MS4A, CD2AP, CD33, and EPHA1 – and contribute to identifying and confirming two other genes, BIN1 and ABCA7, thereby doubling the number of genes known to contribute Alzheimer’s disease.

The researchers’ ultimate aims are two fold. First, identification of new Alzheimer’s disease genes will provide major clues as to its underlying cause. Genetic studies can provide new insights into the molecules at the center of the disease. Gaining this type of understanding is critical for drug discovery since the currently available treatments are only marginally effective.

“The skyrocketing prevalence and financial and societal costs of Alzheimer’s disease will soon undermine the delivery of healthcare worldwide,” said Farrer. “That gives our national research enterprise added incentive to act quickly and boldly to make new discoveries.”

Second, gene discovery of the type highlighted in the Nature Genetics article will contribute to predicting who will develop Alzheimer’s disease, which will be important when preventive measures become available. Knowing these risk genes will also help identify the first disease-initiating steps that begin in the brain long before any symptoms of memory loss or intellectual decline are apparent. This knowledge will help researchers understand the events that lead to the destruction of large parts of the brain and eventually the complete loss of cognitive abilities.

Currently, Alzheimer’s genetics researchers are coming together for an even larger, similar study. The Alzheimer’s Association in the US and the Fondation Plan Alzheimer in France have funded the formation of the International Genomics of Alzheimer’s Project, whose members met for the first time in November 2010 in Paris.

The research published in Nature Genetics was supported by the National Institute on Aging, part of the National Institutes of Health, which includes 29 Alzheimer’s Disease Centers, the National Alzheimer’s Coordinating Center, the NIA Genetics of Alzheimer’s Disease Data Storage Site, the NIA Late Onset Alzheimer’s Disease Family Study and the National Cell Repository for Alzheimer’s Disease. These Centers collect, store and make available to qualified researchers DNA samples, datasets containing biomedical and demographic information about participants, and genetic analysis data.

The findings from the current issue of Nature Genetics can be found here.

April 2, 2009

Sam Thiagalingam’s Lab produces cover and story for Cancer Biology & Therapy
The members of Sam Thiagalingam’s lab have have created the cover graphic for the current issue of Cancer Biology & Therapy.  The issue spotlights their research regarding interaction between p53 and hBub1 in response to spindle checkpoint (SAC) activation.  For more information about the research discoveries and the cover image, navigate to the webpage for the current issue.

March 10, 2009

Researchers from Genetics Program discover Gene Associated with Cocaine Dependence
A reasearch group including members of the BUSM Genetics Program have discovered that the MANEA gene is associated with coacaine dependence and cocaine-induced paranoia.  The findings, discovered through research in collaboration with the Yale University School of Medicine and University of Connecticut School of Medicine, were published in the March issue of the Archives of General PsychiatryMore information is available here.

March 7, 2014
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