Spatial and temporal analysis of Barmah Forest virus disease in Queensland, Australia

Barmah Forest virus (BFV) disease is one of the most widespread mosquito-borne diseases in Australia. The number of outbreaks and the incidence rate of BFV in Australia have attracted growing concerns about the spatio-temporal complexity and underlying risk factors of BFV disease. A large number of notifications has been recorded continuously in Queensland since 1992. Yet, little is known about the spatial and temporal characteristics of the disease. I aim to use notification data to better understand the effects of climatic, demographic, socio-economic and ecological risk factors on the spatial epidemiology of BFV disease transmission, develop predictive risk models and forecast future disease risks under climate change scenarios. Computerised data files of daily notifications of BFV disease and climatic variables in Queensland during 1992-2008 were obtained from Queensland Health and Australian Bureau of Meteorology, respectively. Projections on climate data for years 2025, 2050 and 2100 were obtained from Council of Scientific Industrial Research Organisation. Data on socio-economic, demographic and ecological factors were also obtained from relevant government departments as follows: 1) socio-economic and demographic data from Australian Bureau of Statistics; 2) wetlands data from Department of Environment and Resource Management and 3) tidal readings from Queensland Department of Transport and Main roads. Disease notifications were geocoded and spatial and temporal patterns of disease were investigated using geostatistics. Visualisation of BFV disease incidence rates through mapping reveals the presence of substantial spatio-temporal variation at statistical local areas (SLA) over time. Results reveal high incidence rates of BFV disease along coastal areas compared to the whole area of Queensland. A Mantel-Haenszel Chi-square analysis for trend reveals a statistically significant relationship between BFV disease incidence rates and age groups (ƒÓ2 = 7587, p<0.01). Semi-variogram analysis and smoothed maps created from interpolation techniques indicate that the pattern of spatial autocorrelation was not homogeneous across the state. A cluster analysis was used to detect the hot spots/clusters of BFV disease at a SLA level. Most likely spatial and space-time clusters are detected at the same locations across coastal Queensland (p<0.05). The study demonstrates heterogeneity of disease risk at a SLA level and reveals the spatial and temporal clustering of BFV disease in Queensland. Discriminant analysis was employed to establish a link between wetland classes, climate zones and BFV disease. This is because the importance of wetlands in the transmission of BFV disease remains unclear. The multivariable discriminant modelling analyses demonstrate that wetland types of saline 1, riverine and saline tidal influence were the most significant risk factors for BFV disease in all climate and buffer zones, while lacustrine, palustrine, estuarine and saline 2 and saline 3 wetlands were less important. The model accuracies were 76%, 98% and 100% for BFV risk in subtropical, tropical and temperate climate zones, respectively. This study demonstrates that BFV disease risk varied with wetland class and climate zone. The study suggests that wetlands may act as potential breeding habitats for BFV vectors. Multivariable spatial regression models were applied to assess the impact of spatial climatic, socio-economic and tidal factors on the BFV disease in Queensland. Spatial regression models were developed to account for spatial effects. Spatial regression models generated superior estimates over a traditional regression model. In the spatial regression models, BFV disease incidence shows an inverse relationship with minimum temperature, low tide and distance to coast, and positive relationship with rainfall in coastal areas whereas in whole Queensland the disease shows an inverse relationship with minimum temperature and high tide and positive relationship with rainfall. This study determines the most significant spatial risk factors for BFV disease across Queensland. Empirical models were developed to forecast the future risk of BFV disease outbreaks in coastal Queensland using existing climatic, socio-economic and tidal conditions under climate change scenarios. Logistic regression models were developed using BFV disease outbreak data for the existing period (2000-2008). The most parsimonious model had high sensitivity, specificity and accuracy and this model was used to estimate and forecast BFV disease outbreaks for years 2025, 2050 and 2100 under climate change scenarios for Australia. Important contributions arising from this research are that: (i) it is innovative to identify high-risk coastal areas by creating buffers based on grid-centroid and the use of fine-grained spatial units, i.e., mesh blocks; (ii) a spatial regression method was used to account for spatial dependence and heterogeneity of data in the study area; (iii) it determined a range of potential spatial risk factors for BFV disease; and (iv) it predicted the future risk of BFV disease outbreaks under climate change scenarios in Queensland, Australia. In conclusion, the thesis demonstrates that the distribution of BFV disease exhibits a distinct spatial and temporal variation. Such variation is influenced by a range of spatial risk factors including climatic, demographic, socio-economic, ecological and tidal variables. The thesis demonstrates that spatial regression method can be applied to better understand the transmission dynamics of BFV disease and its risk factors. The research findings show that disease notification data can be integrated with multi-factorial risk factor data to develop build-up models and forecast future potential disease risks under climate change scenarios. This thesis may have implications in BFV disease control and prevention programs in Queensland.

Associations between socioeconomic position, food insecurity and BMI

Introduction: Food insecurity is a social determinant of health and is defined as limited ability to access sufficient amounts of nutritionally adequate or safe food for a healthy and active life. Food insecurity is associated with poor health status and the exacerbation of other health inequalities. This study examined whether an association existed between 1) socioeconomic position (SEP) and food insecurity and 2) food insecurity and weight status. Methods: Data from the 1995 National Nutrition Survey was analysed. A random sample of households (n = 13 858) were asked about dietary habits and food choices. Information about gender, age, BMI, waist circumference, household income and whether the household had run out of money to purchase food in the previous 12 months was obtained and analysed using chi-square and logistic regression. Results: Income was significantly associated with food insecurity; households with lower income were at higher risk of food insecurity. Lower income males were nine times more likely to experience food insecurity and lower income females were three times more likely to experience food insecurity than their higher income counterparts. Food insecurity was significantly associated with body mass index (BMI) among women but not men. Women experiencing food insecurity were at higher risk of overweight/obesity according to BMI and waist circumference measures. Conclusion: Evidence suggests that low income households are at higher risk of food insecurity and women who are food insecure are at higher risk of being overweight or obese. Food insecurity may mediate the association between SEP and BMI.

Does food insecurity contribute to socioeconomic inequalities in BMI?

Introduction: Food insecurity is a social determinant of health and is defined as limited ability to access sufficient amounts of nutritionally adequate or safe food for a healthy and active life. Food insecurity is associated with poor health status and the exacerbation of other health inequalities. This study examined whether an association existed between 1) socioeconomic position (SEP) and food insecurity and 2) food insecurity and weight status. Methods: Data from the 1995 National Nutrition Survey was analysed. A random sample of households (n = 13 858) were asked about dietary habits and food choices. Information about gender, age, BMI, waist circumference, household income and whether the household had run out of money to purchase food in the previous 12 months was obtained and analysed using chi-square and logistic regression. Results: Income was significantly associated with food insecurity; households with lower income were at higher risk of food insecurity. Lower income males were nine times more likely to experience food insecurity and lower income females were three times more likely to experience food insecurity than their higher income counterparts. Food insecurity was significantly associated with body mass index (BMI) among women but not men. Women experiencing food insecurity were at higher risk of overweight/obesity according to BMI and waist circumference measures. Conclusion: Evidence suggests that low income households are at higher risk of food insecurity and women who are food insecure are at higher risk of being overweight or obese. Food insecurity may mediate the association between SEP and BMI.

Potential dietary consquences of food insecurity among Australian adults residing in urbanised disadvantaged areas

Introduction: Food insecurity is the limited/uncertain availability, access to or ability to acquire nutritionally-adequate, culturallyrelevant and safe foods. Adults suffering from food insecurity are at risk of inadequate nutrient intakes or, paradoxically, overweight/ obesity and the development of chronic disease. Despite the global financial crisis and rising costs of living, there are few studies investigating the potential dietary consequences of food insecurity among the Australian population. This study examined whether food insecurity was associated with weight status and poorer intakes of fruits, vegetable and takeaway foods among adults residing in socioeconomically-disadvantaged urbanised areas. Methods: In this cross-sectional study, a random sample of residents (n=1000) were selected from the most disadvantaged suburbs of Brisbane city (response rate 51%). Data were collected by postal questionnaire which ascertained information on sociodemographic information, household food security status, height, weight, fruit and vegetable intakes and takeaway consumption. Data were analysed using chi-square and logistic regression. Results: The overall prevalence of food insecurity was 31%. Food insecurity was not associated with weight status among men or women. Associations between food security status and potential dietary consequences differed for men and women. Among women, food security was not associated with intakes of fruit, vegetable or takeaway consumption. Contrastingly, among men food security was associated with vegetable intakes and consumption of takeaway food: men reporting food insecurity had lower intakes of vegetables and were more likely to consume takeaway foods compared to those that were food secure. Conclusion: Food security is an important public health issue in Australia and has potential dietary consequences that may adversely affect the health of food-insecure groups, most notably men residing in food-insecure households.

An ingenuous Decision Support System (iDSS) approach for remote area pregnant women

This paper addresses development of an ingenious decision support system (iDSS) based on the methodology of survey instruments and identification of significant variables to be used in iDSS using statistical analysis. A survey was undertaken with pregnant women and factorial experimental design was chosen to acquire sample size. Variables with good reliability in any one of the statistical techniques such as Chi-square, Cronbach’s α and Classification Tree were incorporated in the iDSS. The ingenious decision support system was implemented with Visual Basic as front end and Microsoft SQL server management as backend. Outcome of the ingenious decision support system include advice on Symptoms, Diet and Exercise to pregnant women.

Evaluation of the Suchey-Brooks Method of age estimation in an Australian subpopulation using computed tomography of the pubic symphyseal surface

Despite the prominent use of the Suchey-Brooks (S-B) method of age estimation in forensic anthropological practice, it is subject to intrinsic limitations, with reports of differential inter-population error rates between geographical locations. This study assessed the accuracy of the S-B method to a contemporary adult population in Queensland, Australia and provides robust age parameters calibrated for our population. Three-dimensional surface reconstructions were generated from computed tomography scans of the pubic symphysis of male and female Caucasian individuals aged 15–70 years (n = 195) in Amira® and Rapidform®. Error was analyzed on the basis of bias, inaccuracy and percentage correct classification for left and right symphyseal surfaces. Application of transition analysis and Chi-square statistics demonstrated 63.9% and 69.7% correct age classification associated with the left symphyseal surface of Australian males and females, respectively, using the S-B method. Using Bayesian statistics, probability density distributions for each S-B phase were calculated, providing refined age parameters for our population. Mean inaccuracies of 6.77 (±2.76) and 8.28 (±4.41) years were reported for the left surfaces of males and females, respectively; with positive biases for younger individuals (<55 years) and negative biases in older individuals. Significant sexual dimorphism in the application of the S-B method was observed; and asymmetry in phase classification of the pubic symphysis was a frequent phenomenon. These results recommend that the S-B method should be applied with caution in medico-legal death investigations of Queensland skeletal remains and warrant further investigation of reliable age estimation techniques.

Nutrition screening and risk factors prior to chemotherapy in cancer patients 65 years and older

Background The largest proportion of cancer patients are aged 65 years and over. Increasing age is also associated with nutritional risk and multi-morbidities—factors which complicate the cancer treatment decision-making process in older patients. Objectives To determine whether malnutrition risk and Body Mass Index (BMI) are associated with key oncogeriatric variables as potential predictors of chemotherapy outcomes in geriatric oncology patients with solid tumours. Methods In this longitudinal study, geriatric oncology patients (aged ≥65 years) received a Comprehensive Geriatric Assessment (CGA) for baseline data collection prior to the commencement of chemotherapy treatment. Malnutrition risk was assessed using the Malnutrition Screening Tool (MST) and BMI was calculated using anthropometric data. Nutritional risk was compared with other variables collected as part of standard CGA. Associations were determined by chi-square tests and correlations. Results Over half of the 175 geriatric oncology patients were at risk of malnutrition (53.1%) according to MST. BMI ranged from 15.5–50.9kg/m2, with 35.4% of the cohort overweight when compared to geriatric cutoffs. Malnutrition risk was more prevalent in those who were underweight (70%) although many overweight participants presented as at risk (34%). Malnutrition risk was associated with a diagnosis of colorectal or lung cancer (p=0.001), dependence in activities of daily living (p=0.015) and impaired cognition (p=0.049). Malnutrition risk was positively associated with vulnerability to intensive cancer therapy (rho=0.16, p=0.038). Larger BMI was associated with a greater number of multi-morbidities (rho =.27, p=0.001. Conclusions Malnutrition risk is prevalent among geriatric patients undergoing chemotherapy, is more common in colorectal and lung cancer diagnoses, is associated with impaired functionality and cognition and negatively influences ability to complete planned intensive chemotherapy.

Physical performance profile of sub-elite juvenile Gaelic Games players and the prevalence of a Relative Age Effect (RAE)

Gaelic Games are the indigenous sports played in Ireland, the most popular being Gaelic football and hurling. The games are contact sports and the physical demands are thought to be similar to those of Australian Rules football, rugby union, rugby league, field hockey, and lacrosse (Delahunt et al., 2011). The difference in chronological age between children in a single age group is known as relative age and its consequences as the RAE, whereby younger players are disadvantaged (Del Campo et al., 2010). The purpose of this study was to describe the physical and performance profile of sub-elite juvenile Gaelic Games players and to establish if a RAE is present in this cohort and any influence physiological moderator variables may have on this. Following receipt of ethical approval (EHSREC11-45), six sub-elite county development squads (Under-14/15/16 age groups, male, n=115) volunteered to partake in the study. Anthropometric data including skin folds and girths were collected. A number of field tests of physical performance including 5 and 20m speed, vertical and broad jump distance, and an estimate of VO2max were carried out. Descriptive data are presented as Mean SD. Juvenile sub-elite Gaelic Games players aged 14.53 0.82 y were 172.87 7.63 cm tall, had a mass of 64.74 11.06 kg, a BMI of 21.57 2.82 kg.m-2 and 9.22 4.78 % body fat. Flexibility, measured by sit and reach was 33.62 6.86 cm and lower limb power measured by vertical and broad jump were 42.19 5.73 and 191.16 25.26 cm, respectively. Participant time to complete 5m, 20m and an agility test (T-Test) was 1.12 0.07, 3.31 0.30 and 9.31 0.55 s respectively. Participant’s estimated VO2max was 48.23 5.05 ml.kg.min-1. Chi-Square analysis of birth month by quartile (Q1 = January-March) revealed that a RAE was present in this cohort, whereby an over-representation of players born in Q1 compared with Q2, Q3 and Q4 was evident (2 = 14.078, df = 3, p = 0.003). Kruskal-Wallis analysis of the data revealed no significant difference in any of the performance parameters based on quartile of birth (Alpha level = 0.05).This study provides a physical performance profile of juvenile sub-elite Gaelic Games players, comparable with those of other sports such as soccer and rugby. This novel data can inform us of the physical requirements of the sport. The evidence of a RAE is similar to that observed in other contact sports such as soccer and rugby league (Carling et al, 2009; Till et al, 2010). Although a RAE exists in this cohort, this cannot be explained by any physical/physiological moderator variables. Carling C et al. (2009). Scandinavian Journal of Medicine and Science in Sport 19, 3-9. Delahunt E et al. (2011). Journal of Athletic Training 46, 241-5. Del Campo DG et al. (2010). Journal of Sport Science and Medicine 9, 190-198. Delorme N et al. (2010). European Journal of Sport Science 10, 91-96. Till K et al. (2010). Scandinavian Journal of Medicine and Science in Sports 20, 320-329.

The genetics of endurance : frequency of the ACTN3 R577X variant in Ironman World Championship athletes

Objectives To investigate the frequency of the ACTN3 R577X polymorphism in elite endurance triathletes, and whether ACTN3 R577X is significantly associated with performance time. Design Cross-sectional study. Methods Saliva samples, questionnaires, and performance times were collected for 196 elite endurance athletes who participated in the 2008 Kona Ironman championship triathlon. Athletes were of predominantly North American, European, and Australian origin. A one-way analysis of variance was conducted to compare performance times between genotype groups. Multiple linear regression analysis was performed to model the effect of questionnaire variables and genotype on performance time. Genotype and allele frequencies were compared to results from different populations using the chi-square test. Results Performance time did not significantly differ between genotype groups, and age, sex, and continent of origin were significant predictors of finishing time (age and sex: p < 5 × 10−6; continent: p = 0.003) though genotype was not. Genotype and allele frequencies obtained (RR 26.5%, RX 50.0%, XX 23.5%, R 51.5%, X 48.5%) were found to be not significantly different from Australian, Spanish, and Italian endurance athletes (p > 0.05), but were significantly different from Kenyan, Ethiopian, and Finnish endurance athletes (p < 0.01). Conclusions Genotype and allele frequencies agreed with those reported for endurance athletes of similar ethnic origin, supporting previous findings for an association between 577X allele and endurance. However, analysis of performance time suggests that ACTN3 does not alone influence endurance performance, or may have a complex effect on endurance performance due to a speed/endurance trade-off.

Investigation of homocysteine-pathway-related variants in essential hypertension

Hyperhomocysteinemia (hHcy) has been associated with an increased risk of cardiovascular disease and stroke. Essential hypertension (EH), a polygenic condition, has also been associated with increased risk of cardiovascular related disorders. To investigate the role of the homocysteine (Hcy) metabolism pathway in hypertension we conducted a case-control association study of Hcy pathway gene variants in a cohort of Caucasian hypertensives and age- and sex-matched normotensives. We genotyped two polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR C677T and MTHFR A1298C), one polymorphism in the methionine synthase reductase gene (MTRR A66G), and one polymorphism in the methylenetetrahydrofolate dehydrogenase 1 gene (MTHFD1 G1958A) and assessed their association with hypertension using chi-square analysis. We also performed a multifactor dimensionality reduction (MDR) analysis to investigate any potential epistatic interactions among the four polymorphisms and EH. None of the four polymorphisms was significantly associated with EH and although we found a moderate synergistic interaction between MTHFR A1298C and MTRR A66G, the association of the interaction model with EH was not statistically significant (

Prevalence and characteristics of Indigenous drink-driving convictions in Queensland, Australia

Alcohol-involved accidents are one of the leading contributors towards high injury rates among Indigenous Australians. However, there is limited information available to inform existing policies to change current rates. The study aims to provide information about the prevalence and the characteristics of such behaviour. Drink driving convictions from 2006-2010 were extracted from the Queensland Department of Justice and Attorney General database. Convictions were regrouped by gender, age, Accessibility/Remoteness Index of Australia classification (using court location) and sentence severity. A number of cross tabulations were carried out to identify relationships between variables. Standardised adjusted residuals were calculated for each cell in order to determine cell differences that contributed to the chi-square test results. Analysis revealed there were 9,323 convictions, of which the majority were for offences by males (77.5%). In relation to age, 52.6% of the convictions were of persons under 25 years of age. Age was significantly different across the five regions for males only (χ2=90.8, p<0.001), with a larger number of convictions in the ‘very remote’ region of persons over 40+ years of age. Increased remoteness was linked with high range BAC convictions for both males (χ2=168.4, p<0.001) and females (χ2=22.5, p=0.004). Monetary penalties were the primary sentence received for both males and females in all regions. The findings identify the Indigenous drink driving conviction rate to be 6 times that of the general Queensland rate and indicate that a multipronged approach is needed, with tailored strategies for remote offenders, young adults and offenders with alcohol misuse and dependency issues. Further attention is warranted in this area of road safety.

Investigation of two Wnt signalling pathway single nucleotide polymorphisms in a breast cancer-affected Australian population

In the mammary gland, Wnt signals are strongly implicated in initial development of the mammary rudiments and in the ductal branching and alveolar morphogenesis that occurs during pregnancy. Previously, we identified two Wnt signaling pathway-implicated genes, PPP3CA and MARK4, as having a role in more aggressive and potentially metastatic breast tumors. In this study, we examined two SNPs within PPP3CA and MARK4 in an Australian case-control study population for a potential role in human breast cancers. 182 cases and 180 controls were successfully genotyped for the PPP3CA SNP (rs2850328) and 182 cases and 177 controls were successfully genotyped for the MARK4 SNP (rs2395) using High Resolution Melt (HRM) analysis. Genotypes of randomly selected samples for both SNPs were validated by dye terminator sequencing. Chi-square tests were performed to determine any significant differences in the genotype and allele frequencies between the cases and controls. Chi-square analysis showed no statistically significant difference (p > .05) for genotype frequencies between cases and controls for rs2850328 (χ2 = 1.2, p = .5476) or rs2395 (χ2 = .3, p = .8608). Similarly, no statistical difference was observed for allele frequencies for rs2850328 (χ2 = .68, p = .4108) or rs2395 (χ2 = .02, p = .893). Even though an association of the polymorphisms rs2850328 and rs2395 and breast cancer was not detected in our case-control study population, other variants within the PPP3CA and MARK4 genes may still be associated with breast cancer, as both genes are implicated with processes involved in the disease as well as their mutual partaking in the Wnt signaling pathway.

Analysis of the MTHFR C677T variant with migraine phenotypes

Background The methylenetetrahydrofolate reductase (MTHFR) gene variant C677T has been implicated as a genetic risk factor in migraine susceptibility, particularly in Migraine with Aura. Migraine, with and without aura (MA and MO) have many diagnostic characteristics in common. It is postulated that migraine symptomatic characteristics might themselves be influenced by MTHFR. Here we analysed the clinical profile, migraine symptoms, triggers and treatments of 267 migraineurs previously genotyped for the MTHFR C677T variant. The chi-square test was used to analyse all potential relationships between genotype and migraine clinical variables. Regression analyses were performed to assess the association of C677T with all migraine clinical variables after adjusting for gender. Findings The homozygous TT genotype was significantly associated with MA (P < 0.0001) and unilateral head pain (P = 0.002). While the CT genotype was significantly associated with physical activity discomfort (P < 0.001) and stress as a migraine trigger (P = 0.002). Females with the TT genotype were significantly associated with unilateral head pain (P < 0.001) and females with the CT genotype were significantly associated with nausea (P < 0.001), osmophobia (P = 0.002), and the use of natural remedy for migraine treatment (P = 0.003). Conversely, male migraineurs with the TT genotype experienced higher incidences of bilateral head pain (63% vs 34%) and were less likely to use a natural remedy as a migraine treatment compared to female migraineurs (5% vs 20%). Conclusions MTHFR genotype is associated with specific clinical variables of migraine including unilateral head pain, physical activity discomfort and stress.

Polymorphisms of the SIPA1 gene and sporadic breast cancer susceptibility

Background The novel breast cancer metastasis modulator gene signal-induced proliferation-associated 1 (Sipa1) underlies the breast cancer metastasis efficiency modifier locus Mtes 1 and has been shown to influence mammary tumour metastatic efficiency in the mouse, with an ectopically expressing Sipa1 cell line developing 1.5 to 2 fold more surface pulmonary metastases. Sipa1 encodes a mitogen-inducible GTPase activating (GAP) protein for members of the Ras-related proteins; participates in cell adhesion and modulates mitogen-induced cell cycle progression. Germline SIPA1 SNPs showed association with positive lymph node metastasis and hormonal receptor status in a Caucasian cohort. We hypothesized that SIPA1 may also be correlated to breast carcinoma incidence as well as prognosis. Therefore, this study investigated the potential relationship of SIPA1 and human breast cancer incidence by a germline SNP genotype frequency association study in a case-control Caucasian cohort in Queensland, Australia. Methods The SNPs genotyped in this study were identified in a previous study and the genotyping assays were carried out using TaqMan SNP Genotyping Assays. The data were analysed with chi-square method and the Monte Carlo style CLUMP analysis program. Results Results indicated significance with SIPA1 SNP rs3741378; the CC genotype was more frequently observed in the breast cancer group compared to the disease-free control group, indicating the variant C allele was associated with increased breast cancer incidence. Conclusion This observation indicates SNP rs3741378 as a novel potential sporadic breast cancer predisposition SNP. While it showed association with hormonal receptor status in breast cancer group in a previous pilot study, this exonic missense SNP (Ser (S) to Phe (F)) changes a hydrophilic residue (S) to a hydrophobic residue (F) and may significantly alter the protein functions of SIPA1 in breast tumourgenesis. SIPA1 SNPs rs931127 (5' near gene), and rs746429 (synonymous (Ala (A) to Ala (A)), did not show significant associations with breast cancer incidence, yet were associated with lymph node metastasis in the previous study. This suggests that SIPA1 may be involved in different stages of breast carcinogenesis and since this study replicates a previous study of the associated SNP, it implicates variants of the SIPA1 gene as playing a potential role in breast cancer.

Investigation of the NOTCH3 and TNFSF7 genes on C19p13 as candidates for migraine

To investigate the migraine locus around the C19p13 region through analysis of the NOTCH3 gene (C19p13.2-p13.1), previously shown to be a gene involved in CADASIL and the TNFSF7 gene (C19p13), homologous to the ligands of TNF-alpha and TNF-beta, genes that have previously been associated with migraine. The NOTCH3 gene was analysed by sequencing all exons with known CADASIL mutations in a typical (non-familial hemiplegic) migraine family (MF1) that has previously been shown to be linked to C19p13. The TNFSF7 gene was investigated through SNP association analysis using a matched case-control migraine population. NOTCH3 gene sequencing results for affected members of MF1 proved to be negative for all known sequence variants giving rise to mutations for CADASIL. TNFSF7 gene chi-square results showed non-significant P values across all populations tested against controls, except for the MO subgroup which displayed a possible association with the TNFSF7 SNP (genotype, allele analysis P = 0.036, P = 0.017 respectively). Our results suggest that common migraine is not caused by any known CADASIL mutations in the NOTCH3 gene of interest. However, the TNFSF7 gene displayed signs of involvement in a MO affected population and indicates that further independent studies of this marker are warranted.