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Association Screen Of High Priority Positional Candidate Genes For Migraine
Funder
National Health and Medical Research Council
Funding Amount
$187,521.00
Summary
Typical migraine, is a frequent, debilitating and painful disorder that normally affects people during their most productive years (25% of females and 7.5% of males). The World Health Organization recently identified migraine among the world's top 20 leading causes of disability, with an impact that extends far beyond the suffering individual, to the family and community. Although migraine is highly prevalent in our society, its aetiology remains relatively obscure and there are no laboratory ba ....Typical migraine, is a frequent, debilitating and painful disorder that normally affects people during their most productive years (25% of females and 7.5% of males). The World Health Organization recently identified migraine among the world's top 20 leading causes of disability, with an impact that extends far beyond the suffering individual, to the family and community. Although migraine is highly prevalent in our society, its aetiology remains relatively obscure and there are no laboratory based diagnostic tests that identify those who suffer from the disorder. Twin studies indicate that migraine has a significant genetic component, with heritability estimates of 33-65%. Therefore, in an effort to identify the molecular mechanisms underlying the disorder, we have been looking for genomic regions co-inherited (linked) with migraine. The resulting genome-wide linkage scan involving 756 Australian families found significant evidence for the presence of a novel migraine gene on chromosome 5q21 and highly suggestive evidence for a gene on chromosome 10q22. Importantly, we recently replicated linkage to the 5q21 and 10q22 regions in an independent collection of Australian migraine families. Consequently, these regions hold great promise for identifying migraine susceptibility genes in our sample. Using a bioinformatics computer-assisted search of public databases we have ranked the potential candidature of the genes within the 5q21 and 10q22 regions This project will screen the top 21 candidate genes in 768 cases and 768 controls highly selected for the presence and absence of familial migraine, respectively. Our proposed association screen of high priority genes in two strongly implicated regions has high power to identify genes underlying common migraine susceptibility. Such genes will provide clues to the further elucidation of the complex molecular pathways of migraine and , finally, will help in the development of diagnostic tests and rational treatment strategies.Read moreRead less
Mapping Genes For Typical Migraine Using Twin Families.
Funder
National Health and Medical Research Council
Funding Amount
$439,124.00
Summary
Current evidence suggests multiple genes may underlie susceptibility to the more common forms of migraine. The project will look to see if the these genes provide clues to the further elucidation of the complex molecular pathways of migraine and will help in the development of diagnostic tests and evidence-based treatment strategies.
Statistical Analyses Of Breast Cancer Risks For Australian BRCA1 And BRCA2 Mutation Carriers
Funder
National Health and Medical Research Council
Funding Amount
$424,628.00
Summary
About 10 years ago two genes, called BRCA1 and BRCA2, were discovered. The normal function of these genes is to prevent breast and other cancers from developing. All people have two copies of each gene, one inherited from their mother and one from their father. Women who have inherited a fault in one copy are at increased risk of breast and ovarian cancer. There has been considerable controversy about what their actual cancer risks are, especially about how those risks might depend on their age. ....About 10 years ago two genes, called BRCA1 and BRCA2, were discovered. The normal function of these genes is to prevent breast and other cancers from developing. All people have two copies of each gene, one inherited from their mother and one from their father. Women who have inherited a fault in one copy are at increased risk of breast and ovarian cancer. There has been considerable controversy about what their actual cancer risks are, especially about how those risks might depend on their age. We have already conducted studies on this and have developed the necessary statistical methods to address these issues by analysing data from the families in which there are faulty genes. In this study we propose to use two large Australian studies, one of families with multiple-cases of breast cancer (Kathleen Cuningham Consortium for Research on Familial Breast Cancer; kConFab) and the other of the families of women with breast cancer chosen, irrespective of their family cancer histories, through the Victorian and NSW Cancer Registries (Australian Breast Cancer Family Study; ABCFS). A large amount of work has already been conducted to identify these families and test them for faults in BRCA1 and BRCA2. There are over 350 families who carry faults, making this one of the largest studies of its type in the world. We will check the cancer histories of these families and determine which members have, or are likely to have, inherited a faulty gene. We will then estimate the breast and ovarian cancer risks accurately, and with much more precision, than has been done previously. We will also use these large datasets to develop a simple method to identify which Australian women are most likely to carry a fault in BRCA1 or BRCA2, based on their personal and family cancer histories. This study will assist genetic counsellors inform Australian women who consider mutation testing for BRCA1 and BRCA2 about their cancer risks, and help make breast cancer genetics more cost effective.Read moreRead less
Exploiting SNP Data In Epidemiology And Genetics Through Multivariate Analysis Of Complex Traits
Funder
National Health and Medical Research Council
Funding Amount
$476,981.00
Summary
There is overlap in risk factors across multiple diseases, and some of that overlap is due to genetic factors. The availability of genome-wide DNA data on tens of thousands of patients for multiple diseases and healthy controls allows new questions to be asked and answered. For example, what is the overlap due to genes in disease risk for multiple sclerosis and rheumatoid arthritis? This project will develop and statistical genetic methodology to answer such questions and apply those methods to ....There is overlap in risk factors across multiple diseases, and some of that overlap is due to genetic factors. The availability of genome-wide DNA data on tens of thousands of patients for multiple diseases and healthy controls allows new questions to be asked and answered. For example, what is the overlap due to genes in disease risk for multiple sclerosis and rheumatoid arthritis? This project will develop and statistical genetic methodology to answer such questions and apply those methods to a range of important diseases.Read moreRead less
This study is aimed at identifying genetic variants that influence susceptibility to migraine. We plan to use DNA samples already collected from families with multiple migraine affected individuals and sequence a region on the X chromosome that has previously been identified as harbouring a migraine susceptibility gene. This project will identify gene(s) that contain variants contributing to migraine.
I am a genetic epidemiologist focused on bowel cancer risk. I will develop a comprehensive model to estimate individual cancer risk by studying the effects of personal characteristics, cancer history, genetic factors and family history of cancer using large data sets from international consortia I helped establish. My research will enable targeting of screening to those most at risk and will aid the discovery of new causes for bowel cancer.
Genome-wide Association Study Of Migraine In Women With Endometriosis
Funder
National Health and Medical Research Council
Funding Amount
$320,036.00
Summary
Typical migraine, is a frequent, debilitating and painful disorder that affects people during their most productive years (25% of females and 7.5% of males). Women suffering endometriosis (a painful gynecologic disorder affecting up to 10% of women) are at an increased risk of suffering migraine headaches. Our proposed collection of migraine phenotype data on our endometriosis cohort will facilitate identification of genes underlying both disorders.
Human Genetic Susceptibility To Pulmonary Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$760,432.00
Summary
Tuberculosis (TB) infects about a third of the world population, causing significant disease in 10% of infected individuals. We propose to undertake a genome-wide study to investigate human susceptibility to this devastating disease. Identifying novel gene associations from this study may explain why some people are more vulnerable to TB. Understanding these processes may lead to more effective treatments which is essential for the long term control of disease not only in China, but worldwide
Novel Bioinformatics Methods For Prioritizing Disease-causing INDELs
Funder
National Health and Medical Research Council
Funding Amount
$351,664.00
Summary
This project will build a bioinformatics diagnostic tool for the detection of small insertions and deletions (INDELs) in the human genome, which are the second most abundant class of human genetic variations. INDELs are implicated in many human diseases. Thus, the assessment of INDELs is critical for understanding disease etiology, disease susceptibility, and for interpreting personal genome sequencing data. The goal is to improve disease diagnosis and prevention.
Genetic Analysis Of Migraine And Comorbid Psychiatric Disorders Using Twin Families
Funder
National Health and Medical Research Council
Funding Amount
$554,450.00
Summary
Typical migraine, is a frequent, debilitating and painful disorder that normally affects people during their most productive years (up to 25% of females and 7.5% of males in Western populations). Additionally, several studies have demonstrated a cross-sectional relation between psychiatric disorders (namely anxiety and depression) and migraine in community samples. The World Health Organization (WHO) recently identified migraine and major depression among the world's top 20 leading causes of dis ....Typical migraine, is a frequent, debilitating and painful disorder that normally affects people during their most productive years (up to 25% of females and 7.5% of males in Western populations). Additionally, several studies have demonstrated a cross-sectional relation between psychiatric disorders (namely anxiety and depression) and migraine in community samples. The World Health Organization (WHO) recently identified migraine and major depression among the world's top 20 leading causes of disability, with an impact that extends far past the suffering individual, to the family and community. In both sexes of all ages, depression and migraine are the 1st and 19th leading causes of disability affected life years. Although both migraine and depression are highly prevalent in our society, their aetiologies remain relatively obscure and there are no laboratory based diagnostic tests that identify those who suffer from the disorders. Because so little is known about them, a positional cloning approach is the only feasible way to identify the molecular mechanisms underlying these disorders. This project will collect a sample with sufficient power to perform a genome wide linkage screen to i) identify novel susceptibility genes, and ii) confirm previously reported susceptibility genes for migraine and co-occurring psychiatric disorders. The susceptibility genes identified (and confirmed) in this sample will provide clues to the further elucidation of the complex molecular pathways of migraine (and co-occurring psychiatric disorders) and, finally, will help in the development of diagnostic tests and rational treatment strategies.Read moreRead less