Medicine (Western Health) - Research Publications
Permanent URI for this collection
Search Results
1 - 4 of 4
-
ItemGenome-Wide Association Study Using Extreme Truncate Selection Identifies Novel Genes Affecting Bone Mineral Density and Fracture Risk(PUBLIC LIBRARY SCIENCE, 2011-04)Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55-85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or -4.0 to -1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD-associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies.
-
ItemDoes an increase in body mass index over 10 years affect knee structure in a population-based cohort study of adult women?(BMC, 2010)INTRODUCTION: Although obesity is a modifiable risk factor for knee osteoarthritis (OA), the effect of weight gain on knee structure in young and healthy adults has not been examined. The aim of this study was to examine the relationship between body mass index (BMI), and change in BMI over the preceding 10-year period, and knee structure (cartilage defects, cartilage volume and bone marrow lesions (BMLs)) in a population-based sample of young to middle-aged females. METHODS: One hundred and forty-two healthy, asymptomatic females (range 30 to 49 years) in the Barwon region of Australia, underwent magnetic resonance imaging (MRI) during 2006 to 2008. BMI measured 10 years prior (1994 to 1997), current BMI and change in BMI (accounting for baseline BMI) over this period, was assessed for an association with cartilage defects and volume, and BMLs. RESULTS: After adjusting for age and tibial plateau area, the risk of BMLs was associated with every increase in one-unit of baseline BMI (OR 1.14 (95% CI 1.03 to 1.26) P = 0.009), current BMI (OR 1.13 (95% CI 1.04 to 1.23) P = 0.005), and per one unit increase in BMI (OR 1.14 (95% CI 1.03 to 1.26) P = 0.01). There was a trend for a one-unit increase in current BMI to be associated with increased risk of cartilage defects (OR 1.06 (95% CI 1.00 to 1.13) P = 0.05), and a suggestion that a one-unit increase in BMI over 10 years may be associated with reduced cartilage volume (-17.8 ml (95% CI -39.4 to 3.9] P = 0.10). Results remained similar after excluding those with osteophytes. CONCLUSIONS: This study provides longitudinal evidence for the importance of avoiding weight gain in women during early to middle adulthood as this is associated with increased risk of BMLs, and trend toward increased tibiofemoral cartilage defects. These changes have been shown to precede increased cartilage loss. Longitudinal studies will show whether avoiding weight gain in early adulthood may play an important role in diminishing the risk of knee OA.
-
ItemPrevalence of mood and anxiety disorder in self reported irritable bowel syndrome (IBS). An epidemiological population based study of women(BMC, 2010-08-05)BACKGROUND: Irritable bowel syndrome (IBS) is commonly regarded as a functional disorder, and is hypothesized to be associated with anxiety and depression. This evidence mainly rests on population-based studies utilising self-report screening instruments for psychopathology. Other studies applying structured clinical interviews are generally based on small clinical samples, which are vulnerable to biases. The extant evidence base for an association between IBS and psychopathology is hence not conclusive. The aim of this study was therefore to re-examine the hypothesis using population-based data and psychiatric morbidity established with a structured clinical interview. METHODS: Data were derived from a population-based epidemiological study (n = 1077). Anxiety and mood disorders were established using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP) and the General Health Questionnaire (GHQ-12). Current and lifetime IBS was self-reported. Hypertension and diabetes were employed as comparison groups as they are expected to be unrelated to mental health. RESULTS: Current IBS (n = 69, 6.4%) was associated with an increased likelihood of current mood and/or anxiety disorders (OR = 2.62, 95%CI 1.49 - 4.60). Half the population reporting a lifetime IBS diagnosis also had a lifetime mood or anxiety disorder. Exploratory analyses demonstrated an increased prevalence of IBS across most common anxiety and mood disorders, the exception being bipolar disorder. The association with IBS and symptoms load (GHQ-12) followed a curved dose response pattern. In contrast, hypertension and diabetes were consistently unrelated to psychiatric morbidity. CONCLUSIONS: IBS is significantly associated with anxiety and mood disorders. This study provides indicative evidence for IBS as a disorder with a psychosomatic aspect.
-
ItemCalcaneal ultrasound reference ranges for Australian men and women: the Geelong Osteoporosis Study(SPRINGER LONDON LTD, 2013-04)UNLABELLED: Heel ultrasound is a more portable modality for assessing fracture risk than dual-energy X-ray absorptiometry and does not use ionising radiation. Fracture risk assessment requires appropriate reference data to enable comparisons. This study reports the first heel ultrasound reference ranges for the Australian population. INTRODUCTION: This study aimed to develop calcaneal (heel) ultrasound reference ranges for the Australian adult population using a population-based random sample. METHODS: Men and women aged≥20 years were randomly selected from the Barwon Statistical Division in 2001-2006 and 1993-1997, respectively, using the electoral roll. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI) were measured at the heel using a Lunar Achilles Ultrasonometer. Gender-specific means and standard deviations for BUA, SOS and SI were calculated for the entire sample (men 20-93 years, n=1,104; women 20-92 years, n=914) and for participants aged 20-29 years (men, n=157; women, n=151). Associations between ultrasound measures and age were examined using linear regression. RESULTS: For men, mean±standard deviation BUA, SOS and SI were 118.7±15.8 dB/MHz, 1,577.0±43.7 m/s and 100.5±20.7, respectively; values for women were consistently lower (111.0±16.4 dB/MHz, P<0.001; 1,571.0±39.0 m/s, P=0.001; and 93.7±20.3, P<0.001, respectively). BUA was higher in young men compared with young women (124.5±14.4 vs 121.0±15.1 dB/MHz), but SOS (1,590.1±43.1 vs 1,592.5±35.0 m/s) and SI (108.0±19.9 vs 106.3±17.7) were not. The relationships between age and each ultrasound measure were linear and negative across the age range in men; associations were also negative in women but non-linear. CONCLUSION: These data provide reference standards to facilitate the assessment of fracture risk in an Australian population using heel ultrasound.