Genes and Environment in Common Diseases

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Research into Genes and Environment in Common Diseases is conducted by the Wark Group.

Research Interests

Our approach is underpinned by the Genetic-Environmental Life Course (GELC) Approach to health, disease and functional capacity developed at the World Health Organization. The GELC Approach is a comprehensive conceptual framework that can be used to guide understanding, research and health interventions. It is especially useful when applied to common, chronic, polygenic disorders such as osteoporosis, obesity and hypertension.

Our main area of research is in bone health. We also study determinants of body composition and of blood pressure.

Twin Research Program

Much of this research is conducted within a mixed longitudinal cohort study that has involved more than 2000 female twins and sisters for up to 12 years. These subjects are spread over a wide age range. We obtain extensive health and lifestyle information, and various measures (for example, related to bone, blood pressure and body composition) at multiple visits. We utilise this information in several ways:

• to estimate the genetic and environmental sources of variation in the traits of interest; and
• to quantify and compare the effects of specific factors on the traits of interest (for example, the effects of physical activity, smoking and other lifestyle factors on bone health).

Twins also provide a very powerful approach for intervention trials, as we have shown in studying the skeletal effects of calcium supplementation in adolescent female twins. The genetic-environmental model of fracture risk illustrates our approach to thinking about osteoporosis and fractures.

Studies in other Populations

We also conduct observational and intervention studies in other specific populations, to investigate:

• the effects of physical activity in childhood and in older people;
• the effects of calcium intake in adolescent girls;
• the effects of vitamin D on the risk of falls and fractures in older people in residential care;
• bone health and its determinants in Asian Australians;
• new drug therapies in osteoporosis; and
• major causes of osteoporosis such as glucocorticoid therapy.

Current Projects

Title: Heritability of falls risk: a study in female twins
Project Leader(s): John D. Wark, Keith Hill, Kim Bennell, John Hopper
Research staff: Lynda Paton
Student: Natalie El Haber

Title: Smoking and Bone Health: Studies in twins and a Quitline population
Project Leader(s): John D. Wark, Catherine Segan, Richard Osborne, Caryl Nowson, Philip Sambrook, John Hopper, Peter Ebeling
Research staff: Lynda Paton, Sue Kantor

Title: Genetic and environmental determinants of bone loss at the menopause: a twin study
Project Leader(s): Philip Sambrook, John D. Wark, Markus Seibel, John Hopper
Research staff: Lynda Paton, Sue Kantor
Student: Joanna Mackovey

Title: Bone health in twins discordant for anti-epileptic drug therapy
Project Leader(s): John D Wark, Terence O’Brien
Research staff: Lynda Paton, Sue Kantor
Student: Sandra Petty

Title: Genetic and environmental determinants of hip structural properties: twin studies
Project Leader(s): John D. Wark, Thomas Beck, Caryl Nowson, John Hopper, Heather McKay, Mark Forwood
Research staff: Lynda Paton, Sue Kantor, Lan Li

Title: Twin studies of variation and covariation in bone mineral measures and lean body mass
Project Leader(s): John D. Wark, John Hopper, Caryl Nowson
Research staff: Lynda Paton, Sue Kantor

Title: Sources of variation in total and regional fat mass: twin studies
Project Leader(s): John D. Wark, Caryl Nowson
Research staff: Lynda Paton, Sue Kantor, Lan Li

Title: The vitamin D receptor (VDR) gene and bone health: twin studies
Project Leader(s): John D. Wark, John Hopper, Jeffrey Zajac, Caryl Nowson, Mark Stein
Research staff: Lynda Paton, Rachel Davey, Rob MacInnis

Title: Bone health and fracture risk in Asian Australians
Project Leader(s): John D. Wark, Rosemary Wong, Keith Hill
Research staff: Lynda Paton, Sue Kantor, Lan Li
Students: Tessa Hutabarat, Elizabeth Bond

Title: Evaluation of new therapies in osteoporosis
Project Leader(s): John D. Wark, Robyn Craven
Research staff: Elizabeth Hristov, Christine Dos Santos, Paul Wraight, Sue Kantor

Title: Dancing for bone health
Project Leader(s): Kim Bennell, John D. Wark, Karim Khan
Research staff: Sue Kantor
Student: Bernadette Matthews

Title: Bones for life
Project Leader(s): Kim Bennell, John D. Wark
Research staff: Elin Wee
Students: Karen Bolton, Bernadette Matthews

Title: Strength and endurance of trunk extensor muscles, thoracic range of motion and the role of transversus abdominis in patients with vertebral fractures
Project Leader(s): Kim Bennell, John D. Wark, Nicholas Fazzalari, Tim Wrigley, Paul Hodges
Research staff: Sue Kantor
Student: Andrew Briggs

Title: Effects of a physiotherapy intervention programme on individuals with a history of osteoporotic vertebral fracture
Project Leader(s):Kim Bennell, John D. Wark
Student: Alison Greig

10 Most Significant Publications

(Please note this is only a list of most significant publications from the past six years.)

1. Morris FL, Naughton GA, Gibbs JL, Carlson JS & Wark JD (1997). Prospective ten-month exercise intervention in pre-menarcheal girls: positive effects on bone and lean mass. J Bone Min Res,12:1453–62.
2. Hopper JL, Green R, Nowson C, Young D, Larkins RG & Wark JD (1998). Genetic, common environment, and individual specific components of variance for bone mineral density in 10–26 year-old females: a twin study. Am J Epidemiology, 147:17–29.
3. Guthrie JR, Ebeling PR, Hopper JL, Barrett-Connor E, Dennerstein L, Dudley EC, Burger HG & Wark JD (1998). A prospective study of bone loss in menopausal Australian-born women. Osteoporosis Int, 8:282–90.
4. Bonjour J-P, Couper M, Dutta S, Fracchia G, Gundert-Remy U, Idanpaan-Heikkila J, Ikeda M, Kalache A, Kanis JA, Khaltaev N, Lutwak L, Meirik O, Meunier P, Nakamura T & Wark JD (1998). Guidelines for preclinical evaluation and clinical trials in osteoporosis. WHO, Geneva.
5. Young D, Hopper JL, Macinnins RJ, Nowson CA, Hoang NH & Wark JD (2001). Changes in body composition as determinants of longitudinal changes in bone mineral measures in 8–26 year old female twins. Osteoporosis Int, 12(6):506–15.
6. Margerison C, Paton LM, Nowson C, Hossain SF, Kaymakci B & Wark JD (2002). Hormone replacement therapy and bone mineral density: a co-twin approach. Menopause, 9(6):436-42.
7. Wark JD (2003). Influence of nutrition on bone health: The twin model approach, in Nutritional Aspects of Bone Health. New S & Bonjour JP (ed.), Royal Society of Chemistry, Cambridge.
8. Paton LM, Alexander JL, Nowson C, Margerison C, Frame MG, Kaymakci B & Wark JD (2003). Pregnancy and lactation have no long-term deleterious effect on measures of bone mineral in healthy women: A twin study. The American Journal of Clinical Nutrition, March, 77(3): 707–14.
9. Flicker L, Mead K, MacInnis R, Nowson C, Scherer S, Stein MS, Thomas J, Hopper J & Wark JD (in press). Serum vitamin D and falls in older women in residential care in Australia. Journal of the American Geriatrics Society.
10. MacInnis RJ, Cassar C, Nowson CA, Paton L, Flicker L, Hopper JL, Larkins RG & Wark JD (in press). Determinants of bone density in 30 to 65 year old women: a twin study. Journal of Bone and Mineral Research.