What are the genetic factors involved in determining health and - PowerPoint PPT Presentation

Centre for Genetic Epidemiology & Biostatistics What are the genetic factors involved in determining health and disease in families and in populations? How do they interact with environmental factors? Winthrop Professor Eric Moses Centre Director

CORE ACTIVITIES of the Centre Discovery Validation Translation

DISCOVERY • Genome-wide integrative genomics strategies, with initial emphasis on targeted DNA sequencing of the genome (exome and regulatory regions) in families.. moving to whole genome sequencing at epidemiological scale (Busselton population??) – just $ $.. being done now elsewhere… • Collaboration with local/national/international groups with shared vision and complementary family/population resources • Key functions of the Centre: – study design – development of tools for data/project management – development and application of statistical genetics methods – development and application of bioinformatics

VALIDATION • The development of new medicines for prevention/treatment of common genetic diseases requires knowledge of the gene(s) and associated causal variation • As opposed to rare, monogenic disorders, relatively few causal variants have been identified for common complex diseases – most associated SNPs identified by GWAS are not causal • Rare, non-synonymous coding sequence variants may soon be found to contribute to some of the ‘missing heritability’ in common diseases…often with obvious functional consequences • However, multiple regulatory variants with modest effects will be a large component of heritability – currently developing with UWA Winthrop Prof Lawrie Abraham novel high-throughput methods for functional evaluation of regulatory variation at a genome-wide level

TRANSLATION • Taking validated findings into clinically useful tests and treatments is a major objective • Partnerships between big pharma and academia is real opportunity – eg, GlaxoSmithKline (https://pharmainpartnership.gsk.com/) • Once again also involves collaboration with local/national/international groups with shared vision and complementary family/population resources • Key roles played by the Centre will be: – Study Design – Data/Project Management – Statistical Analysis

Participants & Skills Available Sought Clinical Molecular Genetics Statistical Genetics Local Functional Genetics Bioinformatics Computer Programming Epidemiology Clinical National Statistical Genetics Epidemiology Clinical Molecular Genetics Statistical Genetics International Bioinformatics Computer Programming Epidemiology

Resources & Infrastructure Available Sought Population/family samples and data Supercomputing Local High-throughput genomics Supercomputing National High-throughput genomics Population/family samples and data Internationa Supercomputing l High-throughput genomics

PROGRESS TO DATE • Recruitment of internationally competitive statistical geneticist – Dr Phillip Melton; Texas Biomed, USA • Recruitment of post-doctoral scientists to support molecular and statistical genetics core capabilities – Dr Tegan McNab; UWA – Dr Nina McCarthy; RCSI, Ireland • Reconfigured WA DNA Bank to provide on-going support for existing and new users • Application (Paul White) to NeCTAR for funding to complete development of eResearch tools (eg., The Ark) for data (including genetic) and project management in large studies • Recruitment of outstanding PhD candidate (in NGS bioinformatics) – Juan Manuel Peralta; Texas Biomed, USA • Research collaboration underway on preeclampsia/CVD with Raine Study – visiting PhD scholar Dr Mari Loset from NTNU, Norway

FUTURE PLANS - Research • Initiate pilot studies and seek funding (NIH/NHMRC/philanthropic) for collaborative whole exome/genome sequencing studies in family and population- based cohorts – Preeclampsia (Australia, Norway, Finland, Iceland) – Schizophrenia (Assen Jablensky & Luba Kalaydjieva; WAIMR) – Busselton families (various phenotypes; Alan James, Bill Musk, Matt Knuiman, Jenny Hui & colleagues) • Collaboration/seek funding on preterm birth with School for Women’s and Infants Health at KEMH – John Newnham & Matt Payne (microbiome of amniotic fluid) – Craig Pennell (deep re-sequencing of GWAS hits) • Move existing NHLBI funded CVD project to Centre

FUTURE PLANS - Teaching • Establish new Masters Degree in Genetic Epidemiology & Biostatistics (coursework and research)