Posts tagged GWAS
Articles and news from the latest research reports.
Scientists find 6 new genetic risk factors for Parkinson’s
Using data from over 18,000 patients, scientists have identified more than two dozen genetic risk factors involved in Parkinson’s disease, including six that had not been previously reported. The study, published in Nature Genetics, was partially funded by the National Institutes of Health (NIH) and led by scientists working in NIH laboratories.
"Unraveling the genetic underpinnings of Parkinson’s is vital to understanding the multiple mechanisms involved in this complex disease, and hopefully, may one day lead to effective therapies," said Andrew Singleton, Ph.D., a scientist at the NIH’s National Institute on Aging (NIA) and senior author of the study.
Dr. Singleton and his colleagues collected and combined data from existing genome-wide association studies (GWAS), which allow scientists to find common variants, or subtle differences, in the genetic codes of large groups of individuals. The combined data included approximately 13,708 Parkinson’s disease cases and 95,282 controls, all of European ancestry.
The investigators identified potential genetic risk variants, which increase the chances that a person may develop Parkinson’s disease. Their results suggested that the more variants a person has, the greater the risk, up to three times higher, for developing the disorder in some cases.
"The study brought together a large international group of investigators from both public and private institutions who were interested in sharing data to accelerate the discovery of genetic risk factors for Parkinson’s disease," said Margaret Sutherland, Ph.D., a program director at the National Institute of Neurological Disorders and Stroke (NINDS), part of NIH. "The advantage of this collaborative approach is highlighted in the identification of pathways and gene networks that may significantly increase our understanding of Parkinson’s disease."
To obtain the data, the researchers collaborated with multiple public and private organizations, including the U.S. Department of Defense, the Michael J. Fox Foundation, 23andMe and many international investigators.
Affecting millions of people worldwide, Parkinson’s disease is a degenerative disorder that causes movement problems, including trembling of the hands, arms, or legs, stiffness of limbs and trunk, slowed movements and problems with posture. Over time, patients may have difficulty walking, talking, or completing other simple tasks. Although nine genes have been shown to cause rare forms of Parkinson’s disease, scientists continue to search for genetic risk factors to provide a complete genetic picture of the disorder.
The researchers confirmed the results in another sample of subjects, including 5,353 patients and 5,551 controls. By comparing the genetic regions to sequences on a state-of-the-art gene chip called NeuroX, the researchers confirmed that 24 variants represent genetic risk factors for Parkinson’s disease, including six variants that had not been previously identified. The NeuroX gene chip contains the codes of approximately 24,000 common genetic variants thought to be associated with a broad spectrum of neurodegenerative disorders.
"The replication phase of the study demonstrates the utility of the NeuroX chip for unlocking the secrets of neurodegenerative disorders," said Dr. Sutherland. "The power of these high tech, data-driven genomic methods allows scientists to find the needle in the haystack that may ultimately lead to new treatments."
Some of the newly identified genetic risk factors are thought to be involved with Gaucher’s disease, regulating inflammation and the nerve cell chemical messenger dopamine as well as alpha-synuclein, a protein that has been shown to accumulate in the brains of some cases of Parkinson’s disease. Further research is needed to determine the roles of the variants identified in this study.
Researchers Identify Genetic Marker Linked to OCD
A group of researchers led by Johns Hopkins scientists say they have identified a genetic marker that may be associated with the development of obsessive-compulsive disorder (OCD), whose causes and mechanisms are among the least understood among mental illnesses.
The results of the research are published online May 13 by the journal Molecular Psychiatry.
“If this finding is confirmed, it could be useful,” says study leader Gerald Nestadt, M.D., M.P.H., a professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine and director of Johns Hopkins’ Obsessive-Compulsive Disorder Program. “We might ultimately be able to identify new drugs that could help people with this often disabling disorder, one for which current medications work only 60 to 70 percent of the time.”
Nestadt and his team conducted what is known as a genome-wide association study, scanning the genomes of more than 1,400 people with OCD and more than 1,000 close relatives of people with the mental disorder. A significant association was identified in OCD patients near a gene called protein tyrosine phosphokinase (PTPRD).
OCD is a condition marked by thoughts and images that chronically intrude in the mind and by repetitive behaviors aimed at reducing the associated anxiety. Some of the least disabling forms of the disorder can add an extra hour to the day’s routine, causing distress and interfering with daily life. Some people are so disabled that they can’t leave their homes.
Experts say OCD affects an estimated 1 to 2 percent of the U.S. population, and the World Health Organization has called it one of the more disabling medical conditions worldwide. Antidepressants known as SSRIs work for some people, but not everyone; the same is true of behavioral therapy.
Nestadt says the genome-wide association study findings of a PTRPD-OCD link add to evidence that the genetic region they identified is important. The gene has already been shown in animals to be possibly involved in learning and memory, traits influenced by OCD in humans. Moreover, some cases of attention-deficit hyperactivity disorder (ADHD) have been associated with the gene, and OCD and ADHD have some symptoms in common. He says the gene also works with another gene family, SLITRK, which has also been associated with OCD in animals.
“OCD research has lagged behind other psychiatric disorders in terms of genetics,” Nestadt says. “We hope this interesting finding brings us closer to making better sense of it — and helps us find ways to treat it.”
(Image credit: Jennifer Soo)
New contender for ‘fat gene’ found
Researchers may have been focusing on the wrong gene.
Scientists studying what they thought was a ‘fat gene’ seem to have been looking in the wrong place, according to research published today in Nature. It suggests instead that the real culprit is another gene that the suspected obesity gene interacts with.
In 2007, several genome studies identified mutations in a gene called FTO that were strongly associated with an increased risk of obesity and type 2 diabetes in humans. Subsequent studies in mice showed a link between the gene and body mass. So researchers, including Marcelo Nóbrega, a geneticist at the University of Chicago, thought that they had found a promising candidate for a gene that helped cause obesity.
The mutations were located in non-coding portions of FTO involved in regulating gene expression. But when Nóbrega looked closer, he found that something was amiss. These regulatory regions contained some elements that are specific for the lungs, one of the few tissues in which FTO is not expressed. “This made us pause,” he says. “Why are there regulatory elements that presumably regulate FTO in the tissue where it isn’t expressed?”
This was not the first red flag. Previous attempts to find a link between the presence of the obesity-associated mutations and the expression levels of FTO had been a “miserable failure”, he says. When Nóbrega presented his new results at meetings, he adds that many people came to him to say ‘I just knew there was something wrong here’.
So Nóbrega’s team cast the net wider, looking for genes in the broader neighbourhood of FTO whose expression matched that of the mutations, and found IRX3, a gene about half a million base pairs away. IRX3 encodes a transcription factor — a type of protein involved in regulating the expression of other genes — and is highly expressed in the brain, consistent with a role in regulating energy metabolism and eating behaviour.
When they examined the looping three-dimensional structure of the chromosome on which both genes sit in mice, zebrafish and human cells, they found that the obesity-associated regions in FTO were physically in contact with the promoter (the initial gene sequence which acts as an on/off switch) of IRX3. So the switches that turn on IRX3 are actually located far away from IRX3 itself, inside another gene. “We think of the genome as a linear thing, but it’s really a complex 3D structure that coils back onto itself,” he says.
Distant genes
IRX3 also appeared to be strongly linked with obesity. People with one of the obesity-associated mutations showed higher expression of IRX3, but not FTO, in brain tissue samples, the team found. Nóbrega and his colleagues also found that mice lacking the gene weighed 25–30% less than mice with a functional IRX3 gene; did not gain weight on a high-fat diet; were resistant to metabolic disorders such as diabetes and had more of the energy-burning cells known as brown fat. The same results were seen in mice in which the expression of IRX3 was blocked in the hypothalamus, a brain region known to regulate feeding behaviour and energy balance.
Inês Barroso, a geneticist at the Wellcome Trust Sanger Institute in Hinxton, UK, says that the work answers some of the questions around the biology of the link found in the genome-wide association studies (GWAS). “That’s always the tricky thing; a GWAS gives you an association, but it’s just a marker on the genome, it doesn’t actually say anything about which gene it’s affecting,” she says. “This strongly suggests that mediation of body mass is going to be through IRX3 rather than FTO.”
Nóbrega thinks geneticists should keep in mind this example of unexpected interactions between distant genes when dealing with genetic association studies. “There may be many other cases where people are studying the wrong gene,” he says. “We might be chasing ghosts.”
Genetic analysis reveals insights into the genetic architecture of OCD, Tourette syndrome
An international research consortium led by investigators at Massachusetts General Hospital (MGH) and the University of Chicago has answered several questions about the genetic background of obsessive-compulsive disorder (OCD) and Tourette syndrome (TS), providing the first direct confirmation that both are highly heritable and also revealing major differences between the underlying genetic makeup of the disorders. Their report is being published in the October issue of the open-access journal PLOS Genetics.
"Both TS and OCD appear to have a genetic architecture of many different genes – perhaps hundreds in each person – acting in concert to cause disease,” says Jeremiah Scharf, MD, PhD, of the Psychiatric and Neurodevelopmental Genetics Unit in the MGH Departments of Psychiatry and Neurology, senior corresponding author of the report. “By directly comparing and contrasting both disorders, we found that OCD heritability appears to be concentrated in particular chromosomes – particularly chromosome 15 – while TS heritability is spread across many different chromosomes.”
An anxiety disorder characterized by obsessions and compulsions that disrupt the lives of patients, OCD is the fourth most common psychiatric illness. TS is a chronic disorder characterized by motor and vocal tics that usually begins in childhood and is often accompanied by conditions like OCD or attention-deficit hyperactivity disorder. Both conditions have been considered to be heritable, since they are known to often recur in close relatives of affected individuals, but identifying specific genes that confer risk has been challenging.
Two reports published last year in the journal Molecular Psychiatry (1, 2), with leadership from Scharf and several co-authors of the current study, described genome-wide association studies (GWAS) of thousands of affected individuals and controls. While those studies identified several gene variants that appeared to increase the risk of each disorder, none of the associations were strong enough to meet the strict standards of genome-wide significance. Since the GWAS approach is designed to identify relatively common gene variants and it has been proposed that OCD and TS might be influenced by a number of rare variants, the research team adopted a different method. Called genome-wide complex trait analysis (GCTA), the approach allows simultaneous comparision of genetic variation across the entire genome, rather than the GWAS method of testing sites one at a time, as well as estimating the proportion of disease heritability caused by rare and common variants.
"Trying to find a single causative gene for diseases with a complex genetic background is like looking for the proverbial needle in a haystack,” says Lea Davis, PhD, of the section of Genetic Medicine at the University of Chicago, co-corresponding author of the PLOS Genetics report. “With this approach, we aren’t looking for individual genes. By examining the properties of all genes that could contribute to TS or OCD at once, we’re actually testing the whole haystack and asking where we’re more likely to find the needles.”
Using GCTA, the researchers analyzed the same genetic datasets screened in the Molecular Psychiatry reports – almost 1,500 individuals affected with OCD compared with more than 5,500 controls, and nearly TS 1,500 patients compared with more than 5,200 controls. To minimize variations that might result from slight difference in experimental techniques, all genotyping was done by collaborators at the Broad Institute of Harvard and MIT, who generated the data at the same time using the same equipment. Davis was able to analyze the resulting data on a chromosome-by-chromosome basis, along with the frequency of the identified variants and the function of variants associated with each condition.
The results found that the degree of heritability for both disorders captured by GWAS variants is actually quite close to what previously was predicted based on studies of families impacted by the disorders. “This is a crucial point for genetic researchers, as there has been a lot of controversy in human genetics about what is called ‘missing heritability’,” explains Scharf. “For many diseases, definitive genome-wide significant variants account for only a minute fraction of overall heritability, raising questions about the validity of the approach. Our findings demonstrate that the vast majority of genetic susceptibility to TS and OCD can be discovered using GWAS methods. In fact, the degree of heritability captured by GWAS variants is higher for TS and OCD than for any other complex trait studied to date.”
Nancy Cox, PhD, section chief of Genetic Medicine at the University of Chicago and co-senior author of the PLOS Genetics report, adds, “Despite the fact that we confirm there is shared genetic liability between these two disorders, we also show there are notable differences in the types of genetic variants that contribute to risk. TS appears to derive about 20 percent of genetic susceptibility from rare variants, while OCD appears to derive all of its susceptibility from variants that are quite common, which is something that has not been seen before.”
In terms of the potential impact of the risk-associated variants, about half the risk for both disorders appears to be accounted for by variants already known to influence the expression of genes in the brain. Further investigation of those findings could lead to identification of the affected genes and how the expression changes contribute to the development of TS and OCD. Additional studies in even larger patient populations, some of which are in the planning stages, could identify the biologic pathways disrupted in the disorder, potentially leading to new therapeutic approaches.
(Source: medicalxpress.com)
Genetic breakthrough another step to understanding schizophrenia
A consortium of scientists from 20 countries, including researchers from The University of Western Australia, has made a major breakthrough in understanding the genetic basis of the debilitating disorder, schizophrenia.
More than 175 scientists from 99 institutions across Europe, the United States of America and Australia contributed to a genome-wide association analysis which identified 13 new risk loci for schizophrenia.
In an article published in the journal, Nature Genetics, the study authors write that the results provide deeper insight into the genetic architecture of schizophrenia than ever before achieved, and provide a pathway to further research.
"For the first time, there is a clear path to increased knowledge of the etiology of schizophrenia through the application of standard, off-the-shelf genomic technologies for elucidating the effects of common variation," the authors wrote.
Schizophrenia is a complex mental disorder which affects about one per cent of people over their lifetime, leading to prolonged or recurrent episodes that impair severely social functioning and quality of life.
In terms of the ‘global burden of disease and disability’ index, developed by the World Health Organization, it ranks among the top 10 disorders, along with cancer, heart disease, diabetes and other non-communicable diseases.
Winthrop Professor Assen Jablensky, director of UWA’s Centre for Clinical Research in Neuropsychiatry (CCRN) at Graylands Hospital, and Professor Luba Kalaydjieva, of the UWA-affiliated Western Australian Institute for Medical Research (WAIMR), led the UWA research team which took part in the study.
Professor Jablensky said that while a strong genetic component in the causation of schizophrenia had been well established, the role of specific genes and the mechanisms of their regulation remained largely unknown.
"Until recently, results of genetic linkage and association studies could explain only a small fraction of the estimated heritability of the disorder and of its ‘genetic architecture’," Professor Jablensky said.
However recent technological advances, enabling efficient coverage of the entire human genome with millions of single nucleotide polymorphisms (SNPs) as genetic markers, had given rise to a new generation of genome-wide association studies (GWAS), which trace the DNA differences between people affected with the disease and healthy control individuals.
"Since the effects of individual SNPs are quite tiny, their reliable measurement requires very large samples of adequately diagnosed patients and controls," Professor Jablensky said.
"This recent study reports on a major breakthrough in the understanding of the genetic basis of schizophrenia, achieved through meta-analysis of GWAS datasets contributed by a large international Psychiatric Genomics Consortium (PGC) - which includes the UWA research team."
A WA case-control sample consisting of 893 schizophrenia patients and healthy controls was part of a collection of 21,246 schizophrenia cases and 38,072 controls from 19 research centres and consortia across Europe, Australia and the USA.
The study found that a total of 8300 SNPs contribute to the risk for schizophrenia and account for at least 32 per cent of the variance in liability.
"A particularly important result of this study is that many of these SNPs are located on a molecular pathway involved in neuronal calcium signalling, which suggests a novel pathogenetic link in the causation of schizophrenia and possibly other psychotic disorders," Professor Jablensky said.
He said ongoing and future studies by the UWA research team would aim to further refine the genetic analyses of the WA schizophrenia study (which at present includes 1259 persons), and to test neurobiological hypotheses about the treatment responses of genetically defined subsets of patients.
(Source: news.uwa.edu.au)
Key Molecular Pathways Leading to Alzheimer’s Identified
Key molecular pathways that ultimately lead to late-onset Alzheimer’s disease, the most common form of the disorder, have been identified by researchers at Columbia University Medical Center (CUMC). The study, which used a combination of systems biology and cell biology tools, presents a new approach to Alzheimer’s disease research and highlights several new potential drug targets. The paper was published today in the journal Nature.
Much of what is known about Alzheimer’s comes from laboratory studies of rare, early-onset, familial (inherited) forms of the disease. “Such studies have provided important clues as to the underlying disease process, but it’s unclear how these rare familial forms of Alzheimer’s relate to the common form of the disease,” said study leader Asa Abeliovich, MD, PhD, associate professor of pathology and cell biology and of neurology in the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at CUMC. “Most important, dozens of drugs that ‘work’ in mouse models of familial disease have ultimately failed when tested in patients with late-onset Alzheimer’s. This has driven us, and other laboratories, to pursue mechanisms of the common form of the disease.”
Non-familial Alzheimer’s is complex; it is thought to be caused by a combination of genetic and environmental risk factors, each having a modest effect individually. Using so-called genome-wide association studies (GWAS), prior reports have identified a handful of common genetic variants that increase the likelihood of Alzheimer’s. A key goal has been to understand how such common genetic variants function to impact the likelihood of Alzheimer’s.
In the current study, the CUMC researchers identified key molecular pathways that link such genetic risk factors to Alzheimer’s disease. The work combined cell biology studies with systems biology tools, which are based on computational analysis of the complex network of changes in the expression of genes in the at-risk human brain.
More specifically, the researchers first focused on the single most significant genetic factor that puts people at high risk for Alzheimer’s, called APOE4 (found in about a third of all individuals). People with one copy of this genetic variant have a three-fold increased risk of developing late-onset Alzheimer’s, while those with two copies have a ten-fold increased risk. “In this study,” said Dr. Abeliovich, “we initially asked: If we look at autopsy brain tissue from individuals at high risk for Alzheimer’s, is there a consistent pattern?”
Surprisingly, even in the absence of Alzheimer’s disease, brain tissue from individuals at high risk (who carried APOE4 in their genes) harbored certain changes reminiscent of those seen in full-blown Alzheimer’s disease,” said Dr. Abeliovich. “We therefore focused on trying to understand these changes, which seem to put people at risk. The brain changes we considered were based on ‘transcriptomics’—a broad molecular survey of the expression levels of the thousands of genes expressed in brain.”
Using the network analysis tools mentioned above, the researchers then identified a dozen candidate “master regulator” factors that link APOE4 to the cascade of destructive events that culminates in Alzheimer’s dementia. Subsequent cell biology studies revealed that a number of these master regulators are involved in the processing and trafficking of amyloid precursor protein (APP) within brain neurons. APP gives rise to amyloid beta, the protein that accumulates in the brain cells of patients with Alzheimer’s. In sum, the work ultimately connected the dots between a common genetic factor that puts individuals at high risk for Alzheimer’s, APOE4, and the disease pathology.
Among the candidate “master regulators” identified, the team further analyzed two genes, SV2A and RFN219. “We were particularly interested in SV2A, as it is the target of a commonly used anti-epileptic drug, levetiracetam. This suggested a therapeutic strategy. But more research is needed before we can develop clinical trials of levetiracetam for patients with signs of late-onset Alzheimer’s disease.”
The researchers evaluated the role of SV2A, using human-induced neurons that carry the APOE4 genetic variant. (The neurons were generated by directed conversion of skin fibroblasts from individuals at high risk for Alzheimer’s, using a technology developed in the Abeliovich laboratory.) Treating neurons that harbor the APOE4 at-risk genetic variant with levetiracetam (which inhibits SV2A) led to reduced production of amyloid beta. The study also showed that RFN219 appears to play a role in APP-processing in cells with the APOE4 variant.
Putting Our Heads Together: Canines May Hold Clues to Human Skull Development
Man’s best friend may touch our hearts with their empathy, companionship, playfulness and loyalty, and they may also lead us to a deeper understanding of our heads.
In the article, “The Genetics of Canine Skull Shape Variation,” in the February issue of the Genetics Society of America’s journal, GENETICS, Jeffrey J. Schoenebeck, PhD, and Elaine A. Ostrander, PhD, researchers at the National Human Genome Research Institute (NHGRI), the National Institutes of Health (NIH), review progress in defining the genes and pathways that determine canine skull shape and development that have been made in the eight years since the dog genome was mapped.
The implications of this research extend beyond the interests of dog fanciers and breeders. “Dogs can serve as a model for skull growth and shape determination because the genetic conservation between dogs and humans makes it highly likely that craniofacial development is regulated similarly between both species,” Dr. Schoenebeck said. “These discoveries are important for human health and biology, especially for children born with craniofacial deformities,” Dr. Ostrander, added. In humans these deformities include Apert, Crouzon and Pfeiffer syndromes, where skull bones fuse prematurely causing facial malformations, such as wide-set bulging eyes and broad foreheads, resulting in dental, eye and other physiological problems.
Skull shape is a complex trait, involving multiple genes and their interactions. Thanks to standardized canine breeding, which documents more than 400 breeds worldwide, and their distinct morphological features, researchers can disentangle traits such as skull shape, which in many breeds is a breed-defining variation.
For example, researchers are beginning to identify which genes cause a Bulldog or a Pug to have short pushed-in faces, or brachycephaly, and those that cause Saluki’s or collies to have narrow, elongated snouts, or dolichocephaly. Between these two distinct canine cranium shapes are many variations that are also breed specific but can’t be neatly categorized as brachycephalic or dolichocephalic, such as the rounded skull of the Chihuahua or the downward pointing snout of the Bull terrier. Researchers now use genome-wide association studies (GWAS) to identify loci of interest that may be associated with these kinds of subtle differences.
The use of GWAS in determining genetic variation in dogs is in its infancy. What’s exciting said Dr. Schoenebeck is that with these studies and the tools researchers now have to map these variations “we may find new roles for genes, never before implicated in cranium development” and because similar genes and genetic pathways operate in humans, unexplained craniofacial developmental defects may become better understood.
Identifying the causative genetic mechanisms of these variations in canines offer researchers who study human cranial abnormalities “a way to figure out what sort of genetic variation matters and what doesn’t,” said Dr. Ostrander.
Drs. Schoenbeck and Ostrander clearly show there’s a lot more research to do on craniofacial development in dogs. It is also clear that the connection between us and our canine friends is in our heads as well as our hearts.
(Image: Villemarette)
New stroke gene discovery could lead to tailored treatments
A study led by King’s College London has identified a new genetic variant associated with stroke. By exploring the genetic variants linked with blood clotting – a process that can lead to a stroke – scientists have discovered a gene which is associated with large vessel and cardioembolic stroke but has no connection to small vessel stroke.
Published in the journal Annals of Neurology, the study provides a potential new target for treatment and highlights genetic differences between different types of stroke, demonstrating the need for tailored treatments.
Approximately 152,000 people in Britain have a stroke each year, costing the UK over £8.2 billion. While there are thought to be 1.2 million stroke survivors in the UK, more than half have been left with disabilities that affect their daily lives.
A stroke occurs when the blood supply to the brain is cut off, often due to a blood clot blocking an artery that carries blood to the brain, which then leads to brain cell damage. Coagulation (blood clotting) abnormalities, particularly easy clotting of the blood, are therefore common contributing factors in the development of stroke.
Dr Frances Williams, Senior Lecturer from the Department of Twin Research and Genetic Epidemiology at King’s and lead author of the paper, said: ‘Previous studies have demonstrated the influence of genetic factors on the components of coagulation. The goal of this study was to extend these observations to determine if they were further associated with different types of stroke.’
The research was carried out in three stages. The first consisted of a genome-wide association study (GWAS) in 2100 healthy volunteers which identified 23 independent genetic variants that were involved in coagulation. The second stage examined the 23 variants in 4200 stroke and non-stroke cases from centres across Europe (Wellcome Trust Case Control Consortium 2 and MORGAM collections) and found that a particular mutation on the ABO gene was significantly associated with stroke.
Stage three of the study used the MetaStroke cohort, a project of the International Stroke Genetics Consortium which comprises 8900 stroke cases recruited from centres in the Europe, USA and Australia, whose DNA has been collected and undergone GWA scan. It was confirmed that a variant in the ABO blood type gene was associated with stroke, a finding specific to large vessel and cardioembolic stroke.
Dr Williams said: ‘The discovery of the association between this genetic variant and stroke identifies a new target for potential treatments, which could help to reduce the risk of stroke in the future. It is also significant that no association was found with small vessel disease, as this suggests that stroke subtypes involve different genetic mechanisms which emphasises the need for individualised treatment.’
Scientists deepen genetic understanding of MS
Five scientists, including two from Simon Fraser University, have discovered that 30 per cent of our likelihood of developing Multiple Sclerosis (MS) can be explained by 475,806 genetic variants in our genome. Genome-wide Association Studies (GWAS) commonly screen these variants, looking for genetic links to diseases.
Corey Watson, a recent SFU doctoral graduate in biology, his thesis supervisor SFU biologist Felix Breden and three scientists in the United Kingdom have just had their findings published online in Scientific Reports. It’s a sub-publication of the journal Nature.
An inflammatory disease of the central nervous system, MS is the most common neurological disorder among young adults. Canada has one of the highest MS rates in the world.
Watson and his colleagues recently helped quantify MS genetic susceptibility by taking a closer look at GWAS-identified variants in the major histocompatibility complex (MHC) region in 1,854 MS patients. The region has long been associated with MS susceptibility.
The MS patients’ variants were compared to those of 5,164 controls, people without MS.
They noted that eight percent of our 30-per-cent genetic susceptibility to MS is linked to small DNA variations on chromosome 6, which have also long been associated with MS susceptibility.
The MHC encodes proteins that facilitate communication between certain cells in the immune system. Outside of the MHC, a good majority of genetic susceptibility can’t be nailed down because current studies don’t allow for all variants in our genome to be captured.
“Much of the liability is unaccounted for because current research methods don’t enable us to fully interrogate our genome in the context of risk for MS or other diseases,” says Watson.
The researchers believe that one place to look for additional genetic causes of MS may be in genes that have variants that are rare in the population. “The importance of rare gene variants in MS has been illustrated in two recent studies,” notes Watson, now a postdoctoral researcher at the Mount Sinai School of Medicine in New York.
“But these variants, too, are generally poorly represented by genetic markers captured in GWAS, like the one our study was based on.”
(Source: sfu.ca)
Researchers have long known that individual diseases are associated with genes in specific locations of the genome
Genetics researchers at the University of North Carolina at Chapel Hill now have shown definitively that a small number of places in the human genome are associated with a large number and variety of diseases. In particular, several diseases of aging are associated with a locus which is more famous for its role in preventing cancer.
For this analysis, researchers at UNC Lineberger Comprehensive Cancer Center catalogued results from several hundred human Genome-Wide Association Studies (GWAS) from the National Human Genome Research Institute. These results provided an unbiased means to determine if varied different diseases mapped to common ‘hotspot’ regions of the human genome. This analysis showed that two different genomic locations are associated with two major subcategories of human disease.
“Our team is interested in understanding genetic susceptibility to diseases associated with aging, including cancer,” said PhD student William Jeck, who was first author on the study, published in the journal Aging Cell.