- David Mackey, Lions Eye Institute (DavidMackey@lei.org.au)
- Robert Eikelboom, Ear Sciences Centre, UWA (firstname.lastname@example.org)
- Dr Chris Brennan-Jones, Telethon Kids Institute (email@example.com)
List of investigators
- Andrew Whitehouse, Telethon Kids Institute
- Angela Jacques, UWA & UNDA
- Cheryl Da Costa (MD student),
- Hrehan Hakeem (MD student),
- Samuel Calder, Curtin University
- Dr Sarra Jamieson, Telethon Kids Institute
- Dr Seyhan Yazar (UWA & University of Edinburgh)
- Assoc/Prof Alex Hewitt (University of Tasmania, Tasmania & Centre for Eye Research Australia, Victoria)
- Brisbane Adolescent Twin Study (BATS)
- Prof Elizabeth Milne (Telethon Kids Institute)
- Dr Fred K Chen (Lions Eye Institute)
- Prof Kathryn Rose (University of Technology Sydney, NSW)
- Professor Mingguang He (University of Melbourne)
- Dr Paul Sanfilippo (Centre for Eye Research Australia, Victoria)
- Prof Robyn Lucas (Australian National University, ACT)
- Assoc/Prof Stuart MacGregor (Queensland Institute for Medical Research, Queensland)
- Twin Eye Study in Tasmania (TEST)
- Dr Beate Glaser (Cardiff University, UK)
- Dr Cathy Williams (Cardiff University, UK)
- Prof Chris Hammond (King’s College London, UK)
- Consortium of Refractive Error and Myopia (CREAM)
- International Glaucoma Genetics Consortium (IGGC)
- Dr Joe Dennis (Centre for Cancer Genetic Epidemiology University of Cambridge)
- Dr Kate Northstone (Cardiff University, UK)
- Dr Mats Larsson (Orebro University, Sweden)
- Dr Jo White (Queen Margaret University, Edinburgh),
- De Wet Swanepoel (University of Pretoria)
Overview of the current data resources available in the SIG area
The Senses SIG has access to parent report of ear and hearing problems at age 3 and 6 years, middle ear function (tympanometry) and hearing thresholds at age 6 years. This has enabled the Senses SIG to create various diagnostic criteria for otitis media at 3 and 6 years of age, and hearing loss at 6 years of age.
The cohort had no ocular examination until the 20-year follow-up. However, at ages 3 and 5 years, a study nurse screened participants’ eyes and recorded if they had a gross anomaly. At the 20-year follow-up, each participant had 3-hours long eye examination which included fundus photography, corneal topography, conjunctival UV autofluorescence (CUVAF) photography, measurement ocular biometry and several other tests. Additionally, they completed a questionnaire on their previous ocular history, sun exposure behaviours and family history of eye diseases. At the 22-year follow-up, abridged version of these questions was repeated.
Overview of current/recent SIG activity
There is a core dataset for ear and hearing outcomes for Raine Study participants at 3 and 6 years of age and are conducting a survey of listening habits for Raine Study participants in the 26-year follow-up. Currently the Senses SIG is leading a series of studies to examine the longer term developmental effects of otitis media and hearing loss on developmental outcomes (including language, behavioural and cognitive development) at 5, 8, 12 and 16 years of age.
A short eye examination is now completed on all parents who has attended to the Raine Study Parent Sleep Study. Currently, the Raine Study participants are undergoing the same eye exam at the 26-year follow-up to determine any changes in their vision and eye measures compared to results at the 20-year follow-up. The Vision team of Senses SIG continues to analyse data from 20 and 22 years of age and gather evidence on genetic and environmental risk factors associated with development and progression of many eye diseases including myopia, pterygium, strabismus, keratoconus and glaucoma.
Outline of SIG plans for next 5 years
- Complete and publish analyses of otitis media and hearing loss on long-term developmental outcomes
- Complete data collection from the hearing and listening habits survey for the 26-year follow-up
- To identify genes specifically associated with measures of progression of diagnosed myopia and with development of myopia in young adulthood
- To determine the association of detailed measures of education – including educational attainment, scores and gap year activities – with progression of childhood myopia and development of myopia in young adulthood
- To determine whether there is any association between longer duration and intensity of use of personal electronic devices and risk of later-onset myopia, or childhood myopia progression.
- To determine gene-environment interactions that are important to the progression of childhood myopia and the onset of young adult myopia and to identify the molecular pathways that these genes involve.
Brief list of potential student/early career researcher projects
- Influence of otitis media on later cognitive development in children
- Influence of otitis media and hearing loss on later mental health outcomes in children
- Association of educational attainment with with progression of childhood myopia and development of myopia in young adulthood
- Association between duration and intensity of use of personal electronic devices and risk of later-onset myopia, or childhood myopia progression
Please contact the Senses SIG leaders if you are interested in a research project incorporating Senses data and they will coordinate whom to contact within the group.
Top 5-10 key findings (with reference)
- This study showed that 26.8% of children suffered recurrent otitis media and was the first study to provide prevalence data for this disease in a general Australian paediatric population. Brennan-Jones, C.G., Whitehouse, A.J.O., Park, J., Hegarty, M., Eikelboom, R.H., Swanepoel, D., White, J.D., Jamieson, S.E. Prevalence and risk factors of parent-reported recurrent otitis media during early childhood in the Western Australian Pregnancy Cohort (Raine) Study. Journal of Paediatrics and Child Health, 51(4): 403-9, 2015.
- This study showed that predominant breastfeeding for >6 months is protective against otitis media in children at three years of age but that the protective effect does not extend to children at six years of age, where other social and environmental factors may be stronger predictors of otitis media. Brennan-Jones, C.G., Eikelboom, R.H., Jacques, A., Swanepoel, D., Atlas, M.D., Whitehouse, A.J.O., Jamieson, S.E., Oddy, W.H. Predominant breastfeeding for the first six months of life is protective against middle ear effusion in early childhood: a prospective birth cohort study. Clinical Otolaryngology, Mar 31, 2016.
- Analysis of genetic profiles from DNA collected in blood samples and data from comprehensive eye assessments in over 45,000 individuals (including Raine participants) identified 24 new gene variants associated with refractive error. (Verhoeven, Virginie J M, Pirro G Hysi, Robert Wojciechowski, Qiao Fan, Jeremy A Guggenheim, René Höhn, Stuart MacGregor, et al. 2013. “Genome-Wide Meta-Analyses of Multiancestry Cohorts Identify Multiple New Susceptibility Loci for Refractive Error and Myopia.” Nature Genetics 45 (3) (March): 314–8. doi:10.1038/ng.2554)
- Eye length is a major determinant of refractive error and thus of myopia. We identified eight markers for eye length and confirmed one previously reported markers. Of the nine genetic markers, five were associated with refractive error in 18 independent cohorts. This study provided the evidence of shared genes between eye length and refractive error, but importantly also suggested that these traits may have unique pathways. (Cheng, C.Y., Schache, M., Ikram, M.K., et al.,(2013). Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error. American Journal of Human Genetics, 93(2):264-77)
- Vitamin D levels in blood samples and eye examination data from Raine participants at 20 years of age found that young adults with myopia had lower vitamin D levels. Vitamin D deficiency was also associated with a higher risk of myopia (Yazar, S., Hewitt, A. W., Black, L. J., McKnight, C. M., Mountain, J. A., Sherwin, J. C., … Mackey, D. A. (2014). Myopia is associated with lower vitamin D status in young adults. Investigative Ophthalmology & Visual Science, 55(7), 4552–9. doi:10.1167/iovs.14-14589.)
- Every 2 years of additional education increases the myopia levels by one diopter thus indicating a causal relationship between myopia and education. (Cuellar-Partida, G., Lu, Y., Kho, P.F., et al., (2016). Assessing the Genetic Predisposition of Education on Myopia: A Mendelian Randomization Study. Genetic Epidemiology, 40(1):66-72.)
- Conjunctival UV autofluoresence (CUVAF) is a quantifiable measure of ocular sun exposure. In the Raine Study, myopia was inversely associated with CUVAF levels further supporting the relationship between myopia and time outdoors (McKnight, C. M., Sherwin, J. C., Yazar, S., Forward, H., Tan, A. X., Hewitt, A. W., Pennell, C. E., et al. (2014). Myopia in young adults is inversely related to an objective marker of ocular sun exposure: The Western Australian Raine Cohort Study. American Journal of Ophthalmology, 158(5), 1079–1085.e2.). However, the following characteristics must be considered when used:  prevalence of CUVAF increases with increasing latitude (toward equator);  although it is largely environmental, genes also play a significant role in its development (Yazar, S., Cuellar-Partida, G., McKnight C.M., Quach-Thanissorn, P., Mountain, J.A., Coroneo, M.T., et al. (2015) Genetic and Environmental Factors in Conjunctival UV autofluorescence. JAMA Ophthalmology, 133(4): 406-12.)
List of indicative recent publications
- Brennan-Jones, C.G., Eikelboom, R.H., Jacques, A., Swanepoel, D., Atlas, M.D., Whitehouse, A.J.O., Jamieson, S.E., Oddy, W.H. Predominant breastfeeding for the first six months of life is protective against middle ear effusion in early childhood: a prospective birth cohort study. Clinical Otolaryngology, Mar 31, 2016.
- Brennan-Jones, C.G., Whitehouse, A.J.O., Park, J., Hegarty, M., Eikelboom, R.H., Swanepoel, D., White, J.D., Jamieson, S.E. Prevalence and risk factors of parent-reported recurrent otitis media during early childhood in the Western Australian Pregnancy Cohort (Raine) Study. Journal of Paediatrics and Child Health, 51(4): 403-9, 2015.
- Swanepoel, D., Eikelboom, R. H., & Margolis, R. H. (2014). Tympanometry Screening Criteria in Children Ages 5‐7 Yr.Journal of the American Academy of Audiology, 25(10), 927-936, 2014.
- Genetically low vitamin D concentrations and myopic refractive error: a Mendelian randomization study. Cuellar-Partida G, Williams KM, Yazar S, Guggenheim JA, Hewitt AW, Williams C, Wang JJ, Kho PF, Saw SM, Cheng CY, Wong TY, Aung T, Young TL, Tideman JWL, Jonas JB; Consortium for Refractive Error and Myopia (CREAM), Mitchell P, Wojciechowski R, Stambolian D, Hysi P, Hammond CJ, Mackey DA, Lucas RM, MacGregor S. Int J Epidemiol. 2017 Jun 6. doi: 10.1093/ije/dyx068
- New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics. Springelkamp H, Iglesias AI, Mishra A, Höhn R, Wojciechowski R, Khawaja AP, Nag A, Wang YX, Wang JJ, Cuellar-Partida G, Gibson J, Bailey JN, Vithana EN, Gharahkhani P, Boutin T, Ramdas WD, Zeller T, Luben RN, Yonova-Doing E, Viswanathan AC, Yazar S, Cree AJ, Haines JL, Koh JY, Souzeau E, Wilson JF, Amin N, Müller C, Venturini C, Kearns LS, Kang JH; NEIGHBORHOOD Consortium, Tham YC, Zhou T, van Leeuwen EM, Nickels S, Sanfilippo P, Liao J, van der Linde H, Zhao W, van Koolwijk LM, Zheng L, Rivadeneira F, Baskaran M, van der Lee SJ, Perera S, de Jong PT, Oostra BA, Uitterlinden AG, Fan Q, Hofman A, Tai ES, Vingerling JR, Sim X, Wolfs RC, Teo YY, Lemij HG, Khor CC, Willemsen R, Lackner KJ, Aung T, Jansonius NM, Montgomery G, Wild PS, Young TL, Burdon KP, Hysi PG, Pasquale LR, Wong TY, Klaver CC, Hewitt AW, Jonas JB, Mitchell P, Lotery AJ, Foster PJ, Vitart V, Pfeiffer N, Craig JE, Mackey DA, Hammond CJ, Wiggs JL, Cheng CY, van Duijn CM, MacGregor S. Hum Mol Genet. 2017 Jan 15;26(2):438-453. doi: 10.1093/hmg/ddw399.
- Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium. Fan Q, Guo X, Tideman JW, Williams KM, Yazar S, Hosseini SM, Howe LD, Pourcain BS, Evans DM, Timpson NJ, McMahon G, Hysi PG, Krapohl E, Wang YX, Jonas JB, Baird PN, Wang JJ, Cheng CY, Teo YY, Wong TY, Ding X, Wojciechowski R, Young TL, Pärssinen O, Oexle K, Pfeiffer N, Bailey-Wilson JE, Paterson AD, Klaver CC, Plomin R, Hammond CJ, Mackey DA, He M, Saw SM, Williams C, Guggenheim JA; CREAM Consortium. Sci Rep. 2016 May 13;6:25853. doi: 10.1038/srep25853.
- Quantification of sun-related changes in the eye in conjunctival ultraviolet autofluorescence images. Huynh E, Bukowska DM, Yazar S, McKnight CM, Mian A, Mackey DA. J Med Imaging (Bellingham). 2016 Jul;3(3):034001. doi: 10.1117/1.JMI.3.3.034001.
- When do myopia genes have their effect? Comparison of genetic risks between children and adults. Tideman JW, Fan Q, Polling JR, Guo X, Yazar S, Khawaja A, Höhn R, Lu Y, Jaddoe VW, Yamashiro K, Yoshikawa M, Gerhold-Ay A, Nickels S, Zeller T, He M, Boutin T, Bencic G, Vitart V, Mackey DA, Foster PJ, MacGregor S, Williams C, Saw SM, Guggenheim JA, Klaver CC; CREAM Consortium. Genet Epidemiol. 2016 Dec;40(8):756-766. doi: 10.1002/gepi.21999.
List of current/recent grants
- 2017-2020; D Mackey, AW Hewitt, C Hammond, S Macgregor, RM Lucas, K Rose et al. Young Adult Myopia Study (YAMS); NHMRC 1121979.
- 2012-2014, D Mackey, C Pennell, A Hewitt, T Young, C Hammond, M Coreneo, S Macgregor. Genome-wide association study (GWAS) for juvenile-onset myopia and its component measures to identify molecular pathways to prevent myopia; NHMRC 1021105.
- 2011; A Tan, CM McKnight, H Forward, Raine Eye Health Study: Ocular biometry and ultraviolet exposure; Ophthalmic Research Institute of Australia.
- 2011; D Mackey, GWAS analysis for Raine eye health Study; Channel 7 Trust Telethon Trust.
- 2011; DA Mackey. The Raine Eye Health Study: An ophthalmic follow-up study of a longitudinal birth cohort at age 21 years; Australian Foundation for the Prevention of Blindness.
- 2010; D Mackey, C William, J Guggenheim, Comparison & mutual replication studies between ALSPAC and Raine eye health Study using vision relation data; UWA Research Collaboration Awards.
Examples of recent media
- Interview for ScienceNetworkWA on recent publication of prevalence rates of otitis media in Raine Study, December 2014 (http://www.sciencewa.net.au/topics/health-a-medicine/item/3232-allergies-day-care-linked-to-kids-ear-infections/3232-allergies-day-care-linked-to-kids-ear-infections
- Interview ScienceNetworkWA for article entitled “Breastfeeding protects children from ear disease” based on findings from our Raine study paper. June 2016. Also published in The West Australian (http://www.sciencewa.net.au/topics/health-a-medicine/item/4224-breastfeeding)