Program in complex trait genomics

Prof Peter Visscher, Prof Naomi Wray and Prof Jian Yang together comprise the executive team of the Program in Complex Trait Genomics Group (PCTG), funded as an NHMRC Program Grant 2017-2021.

The PCTG comprises a critical mass of more than 30 postdoctoral researchers, plus research assistants and students, all supported by external grant funding.

PCTG is structured into five research themes: statistical genomics, systems genomics, psychiatric genomics, MND genomics and genomics of cognitive ageing.

The Wray laboratory focusses on understanding the genetic contribution to psychiatric and neurological disorders. The group specialises in applying new analytical methods of genomic data to provide insights into these complex disorders, with an ultimate goal to improve diagnosis, prognosis and treatments. The lab plays a key role in the international Psychiatric Genomics Consortium and Prof Wray co-leads the sporadic ALS Australia systems genomics consortium (SALSA), funded by the IceBucket Challenge.

The Visscher laboratory specialises in developing methodology that enables analyses aimed at understanding the genetic basis of differences in risk for disease, and other phenotypes between individuals. This research crosses the boundaries of quantitative and statistical genetics, population genetics and human genetics. Applications are diverse but include the study of cognition, cognitive change, and psychiatric and neurological disorders. 

The Yang laboratory works on the interplay of genetics, genomics, statistics and computer science. The group’s research focusses on developing new statistical methods and performing large-scale analyses of high-throughput genetic and genomic data to understand the genetic architecture of complex traits in humans, with specific interests in model traits such as height, and common diseases such as obesity and schizophrenia.

Research projects

Our group is broadly interested in understanding individual differences between people that are caused by genetic factors. Our research programme focuses on methodology in statistical and quantitative genetics and application of new methods and new kinds of genetic & genomic data to answer important scientific questions. Applications include dissection of genetic variation underlying cognition and cognitive change and quantifying and deciphering the genetic architecture of psychiatric disorders.

Complex Trait Genomics

Complex Traits are measures, diseases and disorders that are underpinned by multiple genetic and non-genetic factors. Genomic analyses of human complex traits are characterised by data sets of many (currently up to hundreds of thousands) individuals and many genomic features (can be millions) per individual. A key focus of our research is the generation of new analytical methods and tools, with applications to multi-omics data (software) to develop better analysis, prediction and diagnostic tools from genomic data, mostly implemented into GCTA.

By integration of our method development with disease-focused themes we aim for fast translation to clinically relevant applications, while also allowing other researchers to apply in the full range of disease domains. The fundamental nature of our research, driven by the nature of complex genetic traits and disorders, includes analysis of millions of genomic data points measured on tens to hundreds of thousands of people. Our research is a Big Data problem.

Funding from the Australian National Health and Medical Research Council and from the University of Queensland is provided to maintain and expand capacity in statistical genomics, to train and mentor researchers in statistical genetics applied to complex traits.

Within the University of Queensland we have established a Complex Trait Genomics Alliance linking the groups across the university who work on genetics of complex traits both in humans and other species.

Psychiatric Genomics

Psychiatric genetics, a subfield of behavioral neurogenetics, studies the contribution of genetic factors to risk of disorders such as schizophrenia, autism and major depression. The underlying rationale is that most psychiatric disorders are highly heritable - meaning that a majority of the risk of having a diagnosis is due to genetic factors shared between relatives. The immediate goal of psychiatric genetics is to gain biological insights into the etiology of psychiatric disorders. The ultimate goal is to use that knowledge to inform the development of evidence-based treatments with improved efficacy and fewer side effects. In other words, the goal is to transform parts of psychiatry into a neuroscience-based discipline.

Our research in psychiatric genetics involves the application of novel statistical methods to high-throughput genome-wide datasets, such as that from large genome-wide association studies. A major focus is to better understand the genetic architecture of psychiatric disorders, including genetic overlap between different disorders (i.e. pleiotropy) and genetic and phenotypic heterogeneity within disorders. A related goal is to integrate methylation, RNA expression and other -omics data in order to develop more powerful genomics-based predictors that incorporate variation due to disease-relevant environmental exposures. Three key studies are in collaboration with the CRC for living with autism spectrum disorders, perinatal depression in collaboration with the international PPD ACT consortium, and major depression.

Genomics of Neurological Disease

We have key research themes in Amyotrophic lateral sclerosis (ALS, the most common of the motor neuron diseases, MND) and in Parkinson’s Disease.

ALS is a devastating disease for those affected and their family members. It is an adult-onset, rapidly progressive neurodegenerative disorder that leads to paralysis and death, typically within 2 to 5 years of first symptoms. To date, the most important fundamental insights into the underlying cellular mechanisms have resulted from studies of the known causal mutations. However, >85% of cases do not harbour known ALS mutations and application of new genomics methods is acknowledged as the strategy most likely to drive progress in unlocking the remaining molecular variations that cause and contribute to the disease. This is necessary if we are to address the desperate need for better diagnosis, prognosis and treatment of ALS. Our research exploits genome-wide genetic and epigenetic profiling methods to discover genes and functional pathways that contribute to ALS pathogenesis and progression. We have established the sporadic ALS Australia system genomics consortium (SALSA) to collect consistent clinical data and biological samples across clinics in Australia to underpin future research based on biological samples, including genomics. Our research is fully integrated with the ALS research in Brisbane.

Parkinson’s disease

Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting ~1% of the Australian population aged over 60. Like many common diseases, risk of Parkinson’s can be attributed to a combination of genetic and environmental factors. A handful of genes associated with rare familial forms of parkisonism have been identified, but like ALS, the great majority of cases do not harbour mutations in those genes. Likewise, a number of environmental factors have been associated either increased (e.g. pesticides, heavy metals) or decreased (e.g. smoking, coffee) risk of the disease, but the underlying molecular pathways through which these exposures influence risk are poorly understood. A better understanding of both genetics and environmental factors is essential if we are to improve diagnosis, prognosis and treatment for this devastating condition. We have partnered with Parkinson’s Queensland (Prof. George Mellick) and clinician researchers in Sydney (Prof. Simon Lewis) and New Zealand (Prof. Martin Kennedy) to undertake whole genome genetic and epigenetic analyses of Parkinson’s disease patients and age-matched controls, and we have established collaborations internationally for large-scale meta-analyses of genetic data. Our goals are to identify novel genes and molecular pathways, and to improve understanding of epigenetic changes arising from PD-associated environmental exposures such as smoking and pesticides.

Cognitive Ageing Genomics

There are large differences between people in how they age. Some people have no apparent physical or mental decline when they get older, some develop mild forms of cognitive impairment and yet others develop dementia. CNSG is involved in a number of research projects to study cognitive ageing, from genetic studies on cognitive differences, cognitive decline and dementia to systems genomics approaches to discover biomarkers for ageing. We are a member of the Centre for Cognitive Ageing and Cognitive Epidemiology at the University of Edinburgh. This Centre is directed by Professor Ian Deary with whom we have had a long-standing and productive research collaboration, centred around the Lothian Birth Cohorts (pictured above).

Research training opportunities

Research title: Genetics and genomics of complex traits

Summary of research interests: Virtually all human traits that vary between individuals have unknown genetic and non-genetic factors that contribute to the observed variation – they are called ‘complex traits’. We discover specific factors that explain individual differences between people across a wide range of complex traits; such as risk to common disease, anthropomorphic traits such as height, genomic traits such as gene expression and gene methylation. We are interested in quantifying and dissecting trait variation in the population into genetic and non-genetic factors, and in identifying specific gene variants that contribute to genetic variation. We use large datasets and sophisticated statistical models to address fundamental questions about genetic variation in the human population and to predict individual complex trait phenotypes using genetic and genomic data. The Yang, Wray and Visscher groups form the Complex Trait Genomics Core offering shared training programs based on informal lectures and discussion groups.

Traineeships, honours and PhD projects include

  • Forensic genomics – making predictions about complex traits from biological samples
  • Estimation of genetic variation from whole genome sequence data

Contact: Professor Peter Visscher

+61 7 3346 6348
p.visscher@imb.uq.edu.au


Research title: Quantitative genomics of common disorders of the brain

Summary of research interests: The last five years have seen unprecedented advances in our understanding of the genetics of complex common disorders of the brain. Given the clinical complexity of these disorders, perhaps it is not surprisingly that the empirical data are revealing complex genetic heterogeneity and a genetic architecture of hundreds of genetic variants of small effect. We combine in-house genetic and ‘omic data with publicly available data sets to further understanding of the etiology of disorders of the brain. We use quantitative genetic modelling to add objective evaluation of empirical data – for example, we recently quantified the likely contribution of de novo mutations, to the association between paternal age and psychiatric disorder. The Yang, Wray and Visscher groups form the Complex Trait Genomics Core offering shared training programs based on informal lectures and discussion groups.

Traineeships, honours and PhD projects include

  • Genomics of neurological disorders, particularly motor neurone disease and Parkinson’s disease
  • Genomics of psychiatric disorders, particularly autism spectrum disorders and major depression
  • Quantitative genetic modelling of disease – using theory to understand empirical data

Contact: Professor Naomi Wray

+61 7 3346 6374
n.wray@imb.uq.edu.au


Research title: Integrative analysis of omics data for human complex diseases

Summary of research interests: There are hundreds of millions of people worldwide who suffer from complex diseases such as obesity, type 2 diabetes and schizophrenia. The etiology of these diseases, however, are poorly understood. We focus on developing novel statistical methods to perform integrate analysis of large-scale data from genomics, transcriptomics and epigenomics studies to identify genes and/or functional DNA elements that are critical for the pathogenesis of a disease. The Yang, Wray and Visscher groups form the Complex Trait Genomics Core offering shared training programs based on informal lectures and discussion groups.

Traineeships, honours and PhD projects include

  • Integrative analysis of omics data to identify genes for human complex traits and diseases
  • Developing user-friendly software tools for the analysis of complex traits using omics data

Contact: Professor Jian Yang

+61 7 3346 6393
jian.yang@imb.uq.edu.au


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Profs Yang, Wray and Visscher

Professors Naomi Wray, Peter Visscher and Jian Yang

Group Leaders, Genomics of Development and Disease Division

Investigators, UQ Project Three Billion

Co-Directors, Program in Complex Trait Genomics

Joint Appointments, UQ Queensland Brain Institute

  +61 7 3346 2635  
  naomi.wray@uq.edu.au
  Professor Wray's IMB Researcher Profile
  Professor Visscher's IMB Researcher Profile
  Professor Yang's IMB Researcher Profile
  UQ Project Three Billion
  Program in Complex Trait Genomics


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  Group Leaders

  • Professor Peter Visscher

    Group Leader, Genomics of Development and Disease Division
    Professorial Research Fellow - GL
    Institute for Molecular Bioscience
    Joint Appointment
    Queensland Brain Institute
  • Professor Naomi Wray

    Group Leader, Genomics of Development and Disease Division
    Professorial Research Fellow - GL
    Institute for Molecular Bioscience
    Joint Appointment
    Queensland Brain Institute
  • Professor Jian Yang

    Group Leader, Genomics of Development and Disease Division
    Professorial Research Fellow - GL
    Institute for Molecular Bioscience
    Joint Appointment
    Queensland Brain Institute

  Researchers

  Students

  • Ms Jing Guo

    Higher degree by research (PhD) student
    Institute for Molecular Bioscience
  • Mr Longda Jiang

    Higher degree by research (PhD) student
    Institute for Molecular Bioscience
  • Mr Irfahan Kassam

    Higher degree by research (PhD) student & Adjunct Fellow
    Institute for Molecular Bioscience
  • Mrs Jennifer Pavlides

    Research higher degree (MPhil) student
    Institute for Molecular Bioscience
  • Mr Restu Restuadi

    Higher degree by research (PhD) student
    Institute for Molecular Bioscience
  • Ms Costanza Vallerga

    Higher degree by research (PhD) student
    Institute for Molecular Bioscience
  • Mr Huanwei Wang

    Higher degree by research (PhD) student
    Institute for Molecular Bioscience
  • Ms Ying Wang

    Higher degree by research (PhD) student
    Institute for Molecular Bioscience
  • Mr Yang Wu

    Higher degree by research (PhD) student & Research Officer
    Institute for Molecular Bioscience
  • Mr Angli Xue

    Higher degree by research (PhD) student
    Institute for Molecular Bioscience
  • Mr Qian Zhang

    Higher degree by research (PhD) student
    Institute for Molecular Bioscience

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