ATR Research Services

Since its inception, more than 400 studies have been initiated using the ATR, and each year over the last decade about 10 new studies commenced. Currently there more than 50 active studies recruiting or collecting data, including several major long-term programs. As demonstrated by the examples below, the ATR is used for a wide variety of scientific purposes, including:

• classic biometrical twin and twin family studies attempting to quantify the roles of genetic and environmental causes of variation in traits, and in disease susceptibility;
• co-twin control studies, using twins discordant for specific environmental factors or exposures, and twins discordant for disease outcomes or measures of morbidity;
• intervention studies, in which twins within a pair are randomly allocated to treatment thereby matching naturally for age, sex and genetic susceptibility; and
• longitudinal studies. These approaches use twins to make inferences about the general population, under important assumptions; the ATR also facilitates
• studies of issues relevant specifically to twins, such as: clinical and service provision in twin pregnancies; maternal issues in pregnancy and after delivery; learning difficulties; the inheritance of twinning; the roles of chorionicity and placental factors, and of factors associated with subfertility and its treatment, as determinants of later health and neurodevelopment; and bereavement issues.

The ATR aims to provide an increasingly comprehensive range of services to twin researchers and to undertake activities that will cultivate the strong links between twins, the scientific community, the commercial sector and the general public that are imperatives for ongoing success.

Research Services Provided by the ATR

Recruitment of Study Subjects - The ATR helps recruit study participants from its database of 30,000+ volunteer twin pairs. Over the last five years, on average 900 pairs have been registered per annum, the majority 0-9 year olds. Most researchers seek adult participants in major capital cities, so the ATR maintains a large, under-utilised sample of young twins for future research, while juggling competing demands for limited numbers of adult, urban twins. Typically 25-50% of adults approached will agree to participate, depending on the study protocol.

ATR Research Archive – The ATR has baseline demographic and general health data, collected in 1982, 1984-92, and 1997, and is archiving other past studies, including biospecimen collections.  Researchers will soon be able to use and access a consolidated electronic archive of data compiled from completed and ongoing ATR studies.

ATR Biobank - The ATR is establishing a backed-up Biobank of DNA samples and other biospecimens collected from previous twin studies, including a central inventory of existing biospecimens stored in other laboratories.

Population-based cohorts - The ATR has relied on voluntary recruitment due to practical necessity, but is aware that the consequent ascertainment bias compromises its effectiveness and international competitiveness. It must compete with population-based registries (e.g. in Scandinavia, where ascertainment is through national population registries and health databases and population-wide genetic epidemiological studies are accepted).  In Australia, privacy legislation prevents easy access to twins on a population-basis.  Recent initiatives, financially and intellectually supported by the ATR, have addressed the need for population-based sampling. These include the WATCH (Western Australian Twin Child Health) Cohort and WATR (Western Australian Twin Registry). A new initiative, currently being developed is the match (Mothers and Twin Children) Multiple Twin Pregnancies Cohort.

Long Term Twin Programs

Behaviour Genetics - Behaviour Genetics has been the principal focus of many ATR associated studies led from QIMR. This work has received major past and current funding from NHMRC, NIH and commercial sources. Major findings are a substantial influence of genetic factors on risk of alcoholism, and that this may involve the alcohol dehydrogenase gene. This was one of the first examples of a quantitative trait locus for a complex behavioural trait.

Musculoskeletal Conditions - A multitude of twin studies of bone mineral density (BMD) and magnetic resonance imaging (MRI), including intervention studies, and of other musculoskeletal conditions including rheumatoid arthritis, osteoarthritis and disc degeneration have been conducted. These have received past and current funding from NHMRC and commercial sources.

Attention Deficit Hyperactivity Disorder (ADHD) - A longitudinal study of young twins and their families focussing on Attention Deficit Hyperactivity Disorder (ADHD), with continual funding from NHMRC, has demonstrated the existence of the entity ADHD as a continuum, and has subtypes that breed true. Findings led to the first text book on genetics and ADHD.

Teeth and Face Patterns -   Researchers at the Dental School at the University of Adelaide, funded by NHMRC, have studied the teeth and faces of a cohort of 600 young twin pairs and their siblings for over 10 years. New methods have been developed for acquiring, displaying, storing and analysing these data. Analyses have focused on causes of variation in tooth size and shape, and the accuracy of zygosity determination from dental morphology.

Cardiovascular Disease -   Professor Stephen Harrap and colleagues at The University of Melbourne have conducted an adult twin family study of cardiovascular risk factors, funded by NHMRC and VicHealth. This has resulted in a number of publications. This study has also found evidence for specific genetic variants influencing baldness and is now funded by ARC.

Moliness and Melanoma - The most important known risk factor for melanoma is a high density of melanocytic naevi, or common moles. QIMR researchers showed that variation in moliness is strongly genetically influenced, and genome scans of 274 twin families suggested that a locus on chromosome 9p may account for 33% of variance in flat mole count. Fine mapping studies are underway to try to locate putative genes in other identified chromosomal regions.

Mammographic Density and Breast Cancer - Mammographic density, measured by computer analysis of mammograms, is now established as one of the strongest risk factors for female breast cancer. A twin study of over 600 pairs conducted in Australia and North America found its heritability to be about 60% in both populations. NHMRC have awarded funds for 2004-06 to continue and expand this work (see Part B: Hopper) and a grant application to NIH for gene discovery is under consideration.

Genetics of DZ Twinning - Researchers at QIMR are studying the genetics of DZ twinning, funded by NHMRC and now NIH (USA). DZ twining is inherited and mutations in intra-ovarian growth factors may contribute in some women.