Navigation Links
11 new genetic susceptibility factors for AD discovered through the largest study
Date:10/27/2013

(Boston)-- The largest international study ever conducted on Alzheimer's disease (AD), the I-GAP (International Genomics Alzheimer's Project) consortium has identified 11 new regions of the genome involved in the onset of this neurodegenerative disease. This study gives an overview of the molecular mechanisms underlying the disease, opening up to a better understanding of the pathophysiology of AD. These results detailed currently in Nature Genetics, could not have been obtained without this unique worldwide collaborative effort.

Since 2009, 10 genes for Alzheimer's disease have been identified. However, much of the individual susceptibility to develop the disease remains unexplained. So in February 2011, the leaders of the four largest international research consortia on the genetics of AD joined forces to accelerate the discovery of new genes. Supported in part by the National Institute on Aging (NIA) and other components of the National Institutes of Health (NIH), in less than three years, the IGAP program identified more genes than had been identified over the previous 20 years. They collected genetic data on 74,076 patients and controls from 15 countries and were able to discover 11 new genes in addition to those already known, and identify 13 other genes, yet to be validated.

These 11 new confirmed genes may open new avenues to understanding the causes of AD. For example, one of the most significant associations was found in the region HLA-DRB5/DRB1 major histocompatibility complex. This finding is interesting in several ways. First, it strongly suggests the involvement of the immune system in AD. In addition, this same region has also been associated with two other neurodegenerative diseases, one known to have an immune mechanism, multiple sclerosis and another not previously thought to have a major immune component, Parkinson's disease.

Some of the newly associated genes confirm biological pathways known to be involved in AD, including the amyloid (SORL1, CASS4 ) and tau (CASS4 , FERMT2 ) pathways. The role of the immune response and inflammation (HLA-DRB5/DRB1 , INPP5D , MEF2C ) already implied by previous work (CR1, TREM2) is reinforced, as are the importance of cell migration (PTK2B), lipid transport and endocytosis (SORL1 ). New hypotheses have also emerged related to hippocampal synaptic function (MEF2C , PTK2B), the cytoskeleton and axonal transport (CELF1 , NME8, CASS4) as well as myeloid and microglial cell functions (INPP5D).

Finally, this work demonstrates that, given the complexity of such a disease, only a global collaboration of research efforts will quickly find solutions to tackle this major threat.

The four founding partners in this international consortium are, in alphabetical order, the Alzheimer's Disease Genetics Consortium (ADGC), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE), the European Alzheimer Disease Initiative (EADI) and the Genetic and Environmental Research in Alzheimer Disease (GERAD) consortium.

Boston University and the Framingham Heart Study are well-represented in this landmark international effort. The neurology working group of the Cohorts for Heart and Aging Research in Genomic Epidemiology is led by Sudha Seshadri, MD, professor of neurology at Boston University School of Medicine (BUSM), who is a senior investigator in the Framingham Heart Study and also one of the senior authors on this manuscript. Several other senior investigators, notably Anita L. DeStefano , PhD, professor of biostatistics Boston University School of Public Health (BUSPH) on behalf of CHARGE, and Lindsay A. Farrer, PhD, Chief of Biomedical Genetics and professor of medicine, neurology, ophthalmology, genetics & genomics, epidemiology, and biostatistics at BUSM and BUSPH on behalf of the ADGC, were key investigators in this effort. Farrer co-directs the data analysis effort for the ADGC which includes nearly all of the nation's researchers working on the genetics of AD as well as many investigators and resources of the 29 NIA funded Alzheimer Disease Centers.

"This study clearly demonstrates that there really is strength in numbers to identify genes that individually have a small effect on risk of Alzheimer's," said Farrer. "But it's not the magnitude of the odds ratio that's really important. Each gene we implicate in the disease process adds new knowledge to our understanding of disease mechanism and provides insight into developing new therapeutic approaches, and ultimately these approaches may be more effective in halting the disease since genes are expressed long before clinical symptoms appear and brain damage occurs," he added.

"This landmark international effort has uncovered new pathways and new genes in old pathways that are definitely associated with Alzheimer dementia, but we need to do much work to better understand how exactly these genes work in health and disease, and to perhaps make drugs from these genes and molecules," said Seshadri. "We will continue to mine these results for new insights, even as we include more patients and use new technologies like whole genome sequencing to find more new pathways and genes," she added.

"Alzheimer's is a complex and devastating disorder, and if we are to reach our goal of finding effective therapies to treat it, then collaboration is key," said Neil Buckholtz, PhD, NIA Division of Neuroscience Director. "IGAP's sharing of DNA samples, data sets and scientific insights proves that team concept, and NIA is gratified to have provided the infrastructure and support needed to move the team forward."


'/>"/>

Contact: Gina DiGravio
gina.digravio@bmc.org
617-638-8480
Boston University Medical Center
Source:Eurekalert

Related medicine news :

1. IntegraGen launches ARISk test, a genetic screening tool for autism in high-risk children
2. 2 genetic deletions in human genome linked to the development of aggressive prostate cancer
3. Head, Body Lice Are Genetically Very Similar
4. Certain Genetic Regions May Be Tied to Osteoporosis
5. Study of half siblings provides genetic clues to autism
6. Genetic variants, tobacco exposure and lung cancer risk
7. Research Gets Closer to Genetic Roots of Glaucoma
8. Moffitt researcher awarded GE grant to develop tool to detect breast cancer metastasis genetic risks
9. Genetically modified T cell therapy shown to be safe, lasting in decade-long study of HIV patients
10. Some women may be genetically predisposed to smoking-related hot flashes
11. Genetic abnormalities in benign or malignant tissues predict relapse of prostate cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/28/2017)... ... June 28, 2017 , ... ... recognized for excellence in employee engagement. Omaha-based C&A Industries, a national leader ... Most Engaged Workplaces™ in North America for 2017. The annual award, ...
(Date:6/28/2017)... , ... June 28, 2017 , ... Drs. Steven Crandall, ... TMJ, treatment in Pittsburgh, PA, and Upper St. Clair, PA, without a referral. The ... for restoring the health of the temporomandibular joint and facial muscles that support it. ...
(Date:6/28/2017)... (PRWEB) , ... June 28, 2017 , ... ... and consulting services, is proud to announce the guest speaker lineup* for its ... the National Alliance of Healthcare Purchaser Coalitions; Dr. Keith Fernandez of Privia Health; ...
(Date:6/28/2017)... ... 28, 2017 , ... Eating disorders have the highest mortality rate of any ... person dies as a direct result from an eating disorder in the U.S. As ... The iaedp Foundation meets this challenge by offering what has become the leading certification ...
(Date:6/28/2017)... ... June 28, 2017 , ... ... governance program for mid-market executives as a kick-off to the fifth annual CEO ... 24, 2017 on the University of Pennsylvania campus, followed by the two-day convention, ...
Breaking Medicine News(10 mins):
(Date:6/20/2017)... and LAGUNA HILLS, Calif. , ... of new data that validate the use of MMprofiler ... patients with multiple myeloma (MM). In a poster presentation ... Hematology Association (EHA) in Madrid, Spain ... MMprofiler for identifying high-risk elderly patients. ...
(Date:6/16/2017)... -- Exactly 50 years ago today, the Monterey Pop Festival opened ... the San Francisco "Summer of Love."  To celebrate the anniversary, ... in strategic market research portals that it will begin delivering ... Northern Light,s "Summer of Love (For Our Customers)."  ... ...
(Date:6/13/2017)... WARSAW, Ind. , June 13, 2017 Zimmer ... in musculoskeletal healthcare, today announced that the U.S. Food and ... Letter dated June 3, 2015 relating to its ... "The successful clearance of ... China manufacturing facility is a measure of the ...
Breaking Medicine Technology: