Transcript Document
TRANSLATIONAL GENOMICS Keratoconus – Genes and Risk Factors Tuesday 11th November 2014 A/Professor Paul Baird Ocular Genetics Unit • Keratoconus – the disease • Families • Gene studies • Other risk factors Treatment options and severity of Keratoconus Disease severity mild Treatment options Glasses Contact lenses moderate Toric IOLs X-linking Keratoplasty severe Corneal transplantation We would like to identify risk factors that influence the disease process - Pre-diagnosis - Disease progression - Response to treatment Aetiology Keratoconus is a Complex disease Non genetic factors Genetic factors Eye rubbing Twin studies Allergy Familial aggregation studies Connective tissue dysfunction Genetic studies Contact lens wear Keratoconus study Eye Exam Questionnaire Demographics, Birth history, Ethnicity, Educational Background, Ocular & Medical History, Family history Smoking & Alcohol consumption details Economic burden questionnaire VA, Refraction, Axial Length, Slit Lamp, Keratometry, OCT, Pentacam DNA Sample Venepuncture 2 x 9ml samples Saliva Participants Biometric Measurement Quality of life questionnaire Height, Weight Hip : Waist Keratoconus study – Genetic studies Eye Exam Questionnaire Demographics, Birth history, Ethnicity, Educational Background, Ocular & Medical History, Family history Smoking & Alcohol consumption details Economic burden questionnaire VA, Refraction, Axial Length, Slit Lamp, Keratometry, OCT, Pentacam DNA Sample Genetic studies Venepuncture Participants Saliva Biometric Measurement Quality of life questionnaire Height, Weight Hip : Waist Family studies in Keratoconus Families help us to track down keratoconus disease genes We want to recruit more families where keratoconus is found in multiple family members Identifying Genes in Keratoconus Multiple genes implicated Eg: VSX1, SOD1, ILIB, COL4A3, COL4A4, LOX Few of these replicated (small sample size, different methodologies) More robust findings for: Hepatocyte Growth Factor (HGF) gene Genes involved with central corneal thickness (CCT) Currently identifying other genes using a genome wide approach Risk Factor Questionnaire Age (years) BMI Gender (male) Eye Rubbing Ethnicity Cigarette Smoking Alcohol consumption Diabetes Hypertension Sleep disorder Connective tissue disorder Arthritis Migraine Allergy Hayfever Asthma Eczema Identify genetic variants/other risk factors of interest associated with disease Incorporate data from patient records - Bioinformatic integration of these data Future Directions • Keratoconus appears to have multiple genes and risk factors • Collecting more individuals and families with keratoconus • Exploring the role of the immune system in disease • Put these risk factors together to better understand disease and help improve patient care