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2. The 'woman's point of view' : women parliamentary candidates and electoral culture, 1918-1931

Author

Berry-Waite, L., Thackeray, David, and Toye, Richard

Subjects
women, elections, gender
Abstract

On 21 November 1918, the Parliament (Qualification of Women) Act was passed, which enabled women over the age of twenty-one to stand for parliamentary election. The 1918 General Election saw women stand for parliament for the first time, but the journey to becoming an MP was far from easy. This thesis traces the parliamentary election campaigns of women candidates from 1918 to 1931. This was a pivotal time in history, as the period from 1918 to 1931 was not a story of continuous progress for women. Seventeen women stood in the 1918 General Election, followed by thirty-three in 1922, thirty-four in 1923, and forty-one in 1924. Sixty-nine women contested the 1929 election, but this figure decreased to sixty-two in 1931. During these years, only thirty-three women were elected to the House of Commons, given the multitude of challenges they faced. This thesis offers the first comprehensive study of female parliamentary candidates from 1918 to 1931, through its systematic analysis of candidates' election addresses. Throughout this period, female candidates utilised the concept of the 'woman's point of view', whereby women were believed to have a viewpoint distinctive from that of men, particularly with regards to what were deemed as traditional female concerns, such as the home and social reform. This thesis examines the concept throughout the five chapters and argues that female candidates used conventional assumptions about gender roles in order to gain acceptance for their pioneering activities. However, it must be acknowledged that female candidates were not a homogenous group, and women's political identities in relation to their gender, party and class are explored throughout this study. Indeed, female candidates generally followed the party line, similar to male candidates, although they often combined their party's policies with reference to their gendered experiences. Until now, the election campaigns and experiences of women candidates during the interwar period have received little attention from historians. The historiography has tended to focus on the small number of women who succeeded in becoming MPs and their experiences in the House of Commons, in addition to analysis of the effectiveness of the interwar women's movement. Thus, this study provides new insights into the ways in which female candidates conducted their campaigns, the political promises they made to the electorate, the issues they championed, and how they navigated their political identities. It contributes to the disciplines of women's, gender, and political history, and takes a digital approach to study the language of candidates' election addresses. In doing so, this thesis makes an original contribution to the historiography.

Published
2022

6. Pseudomonas aeruginosa fimL regulates multiple virulence functions by intersecting with Vfr-modulated pathways

Author

Whitchurch, C B, Beatson, S A, Comolli, J C, Jakobsen, T, Sargent, J L, Bertrand, J J, West, J, Klausen, M, Waite, L L, Kang, P J, Tolker-Nielsen, T, Mattick, J S, and Engel, J N

Abstract

Virulence of Pseudomonas aeruginosa involves the co-ordinate expression of a range of factors including type IV pili (tfp), the type III secretion system (TTSS) and quorum sensing. Tfp are required for twitching motility, efficient biofilm formation, and for adhesion and type III secretion (TTS)-mediated damage to mammalian cells. We describe a novel gene (fimL) that is required for tfp biogenesis and function, for TTS and for normal biofilm development in P. aeruginosa. The predicted product of fimL is homologous to the N-terminal domain of ChpA, except that its putative histidine and threonine phosphotransfer sites have been replaced with glutamine. fimL mutants resemble vfr mutants in many aspects including increased autolysis, reduced levels of surface-assembled tfp and diminished production of type III secreted effectors. Expression of vfr in trans can complement fimL mutants. vfr transcription and production is reduced in fimL mutants whereas cAMP levels are unaffected. Deletion and insertion mutants of fimL frequently revert to wild-type phenotypes suggesting that an extragenic suppressor mutation is able to overcome the loss of fimL. vfr transcription and production, as well as cAMP levels, are elevated in these revertants, while Pseudomonas quinolone signal (PQS) production is reduced. These results suggest that the site(s) of spontaneous mutation is in a gene(s) which lies upstream of vfr transcription, cAMP, production, and PQS synthesis. Our studies indicate that Vfr and FimL are components of intersecting pathways that control twitching motility, TTSS and autolysis in P. aeruginosa.

Published
2005

7. The Need for Inter/Subdisciplinary Thinking in Critical Conceptualizations of Displacement

Author

Roast, A, Conlon, D, Garelli, G, and Waite, L

Subjects
Geography, Planning and Development, Earth-Surface Processes
Abstract

Displacement occupies an ambiguous position in contemporary geographical thought. Displacement through gentrification and regeneration has gained prominence in critical urban geography, even as critical migration, border, and citizenship studies have simultaneously produced a robust literature on transnational displacement and internally displaced persons. In response to emerging crises of global and urban order, this article adds to a consideration of displacement—as concept and methodology—through an urging of attention to three drivers common to urban, subnational, and transnational scales of displacement. Our key argument is to suggest an urgent research agenda addressing the different scales and roles of value, choice, and infrastructure, both as drivers in processes of displacement and as points of learning between subdisciplines. Collectively, our work on migration and urban restructuring shows that large-scale development and resettlement projects, labor markets, and extraordinary measures of crisis management generate new ways in which value is extracted from displaced bodies and depeopled places. Against a tendency to index displacement (in both policy and research methodology) as either voluntary or nonvoluntary, we advance a critique of the choice structure of displacement. We further call attention to the infrastructures and technologies through which displacement is moved from a temporary state of exception to an ongoing state of normality. In doing so, we call for the need to rethink the epistemology of displacement and identify the significance of cross-subdisciplinary conversations for this project. 迁移在当代地理学思想中占有模棱两可的地位。尽管移民、边境和公民研究都发表了大量关于跨国迁移和国内迁移者的文章, 中产阶级化和复兴所导致的迁移在批判城市地理学中仍然占据了重要的地位。为了应对新涌现的全球和城市秩序危机, 本文思考了迁移的概念和方法论, 需要关注城市、区域和跨国迁移的三个共同驱动因素。我们提出的紧迫研究议程, 要求研究价值、选择和基础设施的不同规模和作用, 这两者既是迁移过程的驱动因素, 也是各学科之间的学习点。总体来说, 我们在移民和城市重组方面的研究表明, 大规模的开发和安置项目、劳动力市场、非常规的危机管理措施, 产生了从迁移者和无人区榨取价值的新方法。我们反对自愿或非自愿地（在政策和研究方法上）将迁移进行指数化的倾向, 批判了迁移的选择结构。我们进一步呼吁, 应当关注将迁移从暂时的例外状态转变为持续的正常状态的基础设施和技术。由此, 我们认为, 有必要重新思考迁移的认识论、寻求跨学科对话的意义。 La posición que ocupa el desplazamiento en el pensamiento geográfico contemporáneo es ambigua. El desplazamiento, asociado con la gentrificación y la regeneración, ha ganado prominencia en la geografía urbana crítica, incluso cuando los estudios críticos sobre migración, fronteras y ciudadanía han producido de manera simultánea una literatura sólida sobre el desplazamiento transnacional e interno de personas. Respondiendo a las crisis emergentes del orden global y urbano, este artículo contribuye en la consideración del desplazamiento––como concepto y metodología–– formulando un llamado de atención sobre tres factores comunes a las escalas urbanas, subnacionales y transnacionales del desplazamiento. Nuestro argumento central es la sugerencia de una urgente agenda de investigación que aborde las diferentes escalas y funciones del valor, la elección y la infraestructura, tanto como controladores de los procesos de desplazamiento, como puntos de aprendizaje entre subdisciplinas. Colectivamente, nuestro trabajo sobre la migración y la reestructuración urbana muestra que los proyectos de desarrollo y reasentamiento a gran escala, los mercados laborales y las medidas extraordinarias de manejo de crisis, generan nuevas formas de extraer valor de los cuerpos desplazados y de los lugares que quedaron despoblados. Frente a la tendencia a clasificar el desplazamiento (tanto en política como en la metodología de la investigación) como voluntario e involuntario, proponemos una crítica de la estructura de elección del desplazamiento. También, llamamos la atención sobre las infraestructuras y tecnologías a través de las cuales transmuta el desplazamiento de un estado temporal de excepción a un estado continuo de normalidad. Al hacer esto, reclamamos la necesidad de repensar la epistemología del desplazamiento e identificar la importancia de las conversaciones interdisciplinarias para este proyecto.

Published
2022

8. Use of induction of labour and emergency caesarean section and perinatal outcomes in English maternity services: a national hospital-level study

Author

Gurol-Urganci, I, Jardine, J, Carroll, F, Dunn, G, Fremeaux, A, Muller, P, Relph, S, Waite, L, Webster, K, Oddie, S, Hawdon, J, Harris, Tina, Khalil, A, and van der Meulen, J

Subjects
quality, caesarean, Obstetrics and Gynecology, stillbirth, pregnancy, reproductive and urinary physiology, intervention, Induction, labour
Abstract

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. ABSTRACT Objectives – To assess the association between hospital-level rates of induction of labour and emergency caesarean section, as measures of “practice style”, and rates of adverse perinatal outcomes. Design – National study using electronic maternity records. Setting – English National Health Service. Participants – Hospitals providing maternity care to women between April 2015 and March 2017. Main outcome measures – Stillbirth, admission to a neonatal unit, and babies receiving mechanical ventilation. Results – Among singleton term births, the risk of stillbirth was 0.15%; of admission to a neonatal unit 5.4%; and of mechanical ventilation 0.54%. There was considerable between-hospital variation in the induction of labour rate (minimum 17.5%, maximum 40.7%) and the emergency caesarean section rate (minimum 5.6%, maximum 17.1%). Women who gave birth in hospitals with a higher induction of labour rate had better perinatal outcomes. For each 5%-point increase in induction, there was a decrease in the risk of term stillbirth by 9% (OR 0.91; 95% CI 0.85 to 0.97) and mechanical ventilation by 14% (OR 0.86; 95% CI 0.79 to 0.94). There was no significant association between hospital-level induction of labour rates and neonatal unit admission at term (p>0.05). There was no significant association between hospital-level emergency caesarean section rates and adverse perinatal outcomes (p always >0.05). Conclusions – There is considerable between-hospital variation in the use of induction of labour and emergency caesarean section. Hospitals with a higher induction rate had a lower risk of adverse birth outcomes. A similar association was not found for caesarean section.

Published
2022

9. Obstetric interventions and pregnancy outcomes during the Covid-19 pandemic in England: a nationwide cohort study

Author

Gurol-Urganci, I, Waite, L, Webster, K, Jardine, J, Carroll, F, Dunn, G, Fremeaux, A, Harris, T (Presenter), Hawdon, J, Muller, P, van der Meulen, J, and Khalil, A

Subjects
pregnancy outcomes, Covid-19, Interventions
Abstract

Title Obstetric interventions and pregnancy outcomes during the COVID-19 pandemic in England: a nationwide cohort study 300 words excluding title and headings No references Background The COVID-19 pandemic has disrupted maternity services worldwide and imposed restrictions on societal behaviours. The ‘indirect’ effects of these changes on maternal and neonatal outcomes are likely to be larger than the direct effects of COVID-19 infection. Aims and objective/s Comparing obstetric intervention rates and pregnancy outcomes in England during the pandemic/prepandemic periods To assess if the differences in rates varied according to ethnic and socioeconomic background. Method (must include research design, sample, analysis and ethical approval) National study of singleton births in English NHS hospitals. Births during the COVID-19 pandemic period (23/03/20-22/2/21) compared with births during the corresponding calendar period one year earlier. Hospital Episode Statistics provided data about maternal characteristics, obstetric inventions and maternal and neonatal outcomes. Multi-level logistic regression models were used with all models adjusted for maternal characteristics and COVID-19 status at birth. This study was exempt from ethical review as we used routinely collected data; personal data used without individual consent was approved by the NHS Health Research Authority. Findings: Of 948,020 singleton births 451,727 occurred during the defined pandemic period. Maternal characteristics were similar in the pre-pandemic and pandemic periods. Compared to the pre-pandemic period, stillbirth rates remained similar (0.36% versus 0.37% p-value 0.16),preterm birth and SGA birth rates were slightly lower (6.0% versus 6.1% and 6% versus 5.8% respectively, both p

Published
2022

10. National Maternity and Perinatal Audit. Ethnic and Socio-economic inequalities in NHS maternity and perinatal care for women and their babies. Assessing care using data from births between 1 April 2015 and 31 March 2018 across England, Scotland and Wales

Author

NMPA Project Team, Webster, K., Carroll, F., Coe, M., Dunn, G., Fremeaux, A., Gurol-Urganci, I., Jardine, J., Karia, A., Muller, P., Relph, S., Waite, L., Harris, Tina, Hawdon, J., Oddie, S., Khalil, A., and van der Meulen, J.

Subjects
Maternity care, Perinatal care, Ethnicity, Inequalities, Socio economic
Abstract

Executive summary Introduction The purpose of this report is to describe inequalities in maternity and perinatal care for women and their babies in England, Scotland and Wales during the period 1 April 2015 to 31 March 2018. Using routinely collected data, care and outcomes experienced by women and babies using NHS maternity services are measured and stratified by ethnicity and by Index of Multiple Deprivation (IMD), a proxy for socio-economic deprivation. This report focuses on the following maternal measures: ● caesarean birth (presented as elective, emergency and both combined) ● birth without intervention ● major postpartum haemorrhage (1500 ml or more) and the following perinatal measures: ● an Apgar score of less than 7 at 5 minutes ● breast milk at first feed ● neonatal unit admission at term. Methods This report uses existing NMPA linked datasets. Ethnicity is coded using the Office for National Statistics (ONS) 2001 census categorisation of 16+1 codes for ethnicity,2 grouped into white, South Asian, Black and Other (comprising ‘Mixed’ and ‘Other’ combined). Socio-economic deprivation is measured using the Index of Multiple Deprivation (IMD), an area-based measurement of multiple deprivation calculated for each lower-layer super output area (LSOA) in England and Wales, and data zone in Scotland.3 IMD is based on residential postcode and grouped into quintiles of national distribution (quintile 1 = least deprived to quintile 5 = most deprived) for analysis. Results for each maternal and perinatal measure are reported by the mother’s ethnic group and IMD quintile. The results presented in this report are crude and therefore descriptive. The results do not take into account the interactions that contributory factors, such as parity, age, pre-existing co-morbidities, ethnicity and deprivation may have on each other, the complexities of which are not easily interpreted in an audit report such as this. An advisory group comprising professionals and a diverse range of service user representatives with experience of accessing maternity care was involved in the sprint audit. The advisory group was involved in the choice of measures for inclusion in this report, interpretation of results, identifying key messages, and reviewing the draft report and recommendations. Key findings Our results demonstrate differences in outcomes of maternity and perinatal care among women and birthing people, and their babies, via comparisons between those living in the most deprived and the least deprived areas in Great Britain, and in those from ethnic minority groups versus white ethnic groups. Women from South Asian and Black ethnic groups and those from the most deprived areas had higher rates of hypertension and diabetes when compared with women from white ethnic groups and those in the least deprived areas. Smoking was considerably higher among women and birthing people from white ethnic groups and those in the most deprived quintile. Women from Black ethnic groups had a higher rate of experiencing a birth without intervention. While this may be desirable in many situations, it may also represent circumstances where interventions are desired or indicated but do not occur. Rates of caesarean birth (both elective and emergency combined) and rates of emergency caesarean birth were highest for women from Black ethnic groups and higher for women from South Asian groups when compared with those from white ethnic groups. Women and birthing people from Black ethnic groups had higher rates of major postpartum haemorrhage (1500 ml or more) when compared with women and birthing people from white ethnic groups. In contrast to the usual association of increased deprivation with increased morbidity, a decreasing trend for major postpartum haemorrhage (1500 ml or more) was observed from the least to most deprived. Babies born to women from South Asian ethnic groups were less likely to have an Apgar score of less than 7 at 5 minutes but were more likely to be admitted to a neonatal unit at term when compared with babies born to women from white ethnic groups. Babies born to women from Black ethnic groups were more likely to be assessed as having an Apgar score of less than 7 at 5 minutes and were more likely to be admitted to a neonatal unit at term when compared with babies born to women from white ethnic groups. Rates of receiving breast milk at their first feed were significantly lower for babies born to white women and to those living in the most deprived areas. We also found areas of concern with regard to data completeness and rates of missing data by ethnic group and IMD. Our results show 1 in 10 women and birthing people in Great Britain (1 in 5 in Scotland) did not have their ethnic group recorded, and IMD was missing for 6%. Recommendations R1 Target efforts for a life-course approach to improve the health of people, addressing the wider social determinants of health as well as specific health-related risk factors. Offer individualised preconception and antenatal information tailored to their circumstances, including BMI, smoking, pre-existing comorbidities (hypertension and type 2 diabetes) and whether this is their first birth or they have previously had a caesarean birth. (Audience: Healthcare professionals working in maternity services, maternity services providers, general practitioners, primary care providers, public health policy makers) R2 Target efforts to reduce smoking. Audit rates of carbon monoxide testing and referrals for smoking cessation for women during pregnancy, and audit compliance with monitoring for fetal growth restriction. (Audience: Healthcare professionals working in maternity services, maternity services providers, general practitioners, primary care providers, stop smoking services, public health policy makers) R3 Support research and investigation into why women from ethnic minority groups and more deprived areas have higher rates of stillbirth, taking into consideration differences in care, specific risk factors and the wider determinants of health. (Audience: National Institute for Health Research, Health and Care Research Wales and NHS Research Scotland in consultation with the Royal College of Obstetricians and Gynaecologists and policy makers, service planners/commissioners, service managers and healthcare professionals working for maternity services) R4 Improve availability and quality of information about choices during pregnancy and labour, with particular attention to the development of evidence-based shared decision-making tools for place, mode and timing of birth and pain relief options. Consider using the IDECIDE tool (when available). (Audience: Healthcare professionals working in maternity services, maternity services providers, NHS England, NHS Scotland, NHS Wales) R5 Avoid term admissions to a neonatal unit through improving transitional care provision, by establishing facilities where they are not currently available; or in hospitals that do have transitional care facilities, by expanding cot space availability and increasing numbers of appropriately trained staff. (Audience: Maternity and neonatal services providers) R6 Offer all women breastfeeding information and support, and target support in specific areas where breastfeeding rates are lowest (see also Priority 4c, intervention 3 of the Equity and Equality: Guidance for Local Maternity Systems). (Audience: Healthcare professionals working in maternity services, health visitors, primary care providers, maternity care services) R7 Review equality and diversity training provision and update to include the risks associated with deprivation, and how to recognise and avoid unconscious bias (see also Priority 4d, intervention 1 of the Equity and Equality: Guidance for Local Maternity Systems). (Audience: Local trusts and health boards, medical Royal Colleges, Royal Colleges of Nursing and Midwifery, General Medical Council, Nursing and Midwifery Council, Health and Care Professions Council, higher education institutions) R8 Ethnicity should be asked of and accurately recorded for all pregnant people using agreed ethnic group coding systems that should be updated regularly in accordance with the most current census groups. Consideration should be given to methods for self-reporting of ethnicity whenever possible (see also Priority 3, intervention 1 of the Equity and Equality: Guidance for Local Maternity Systems). (Audience: Healthcare professionals working in maternity services, maternity service providers, general practitioners, primary care providers, NHS England, NHS Scotland, NHS Wales) R9 Review the ethnic diversity and rates of socio-economic deprivation in the local area of each NHS trust or board and consider ways to reduce inequalities in healthcare outcomes (see also Priority 4, intervention 1 of the Equity and Equality: Guidance for Local Maternity Systems). (Audience: Local trusts and health boards, primary care providers, public health bodies, local government) R10 Prioritise further research in NHS maternity and perinatal care that could improve outcomes for women, and their babies, from ethnic minority groups and those in the most deprived areas. Undertaking quantitative analysis to investigate ethnic and socio-economic inequalities and report on the mediating factors and causal pathways; along with qualitative research to include exploring the experiences of people accessing maternity care. (Audience: National Institute for Health Research, UK Research and Innovation, Health and Care Research Wales and NHS Research Scotland in consultation with the Royal College of Obstetricians and Gynaecologists and policy makers, service planners/commissioners, service managers and healthcare professionals working for maternity services

Published
2021

12. Clinical Report 2021: Based on births in NHS maternity services in England, Scotland and Wales between 1 April 2017 and 31 March 2018

Author

Carroll, F., Coe, M., Dunn, G., Fremeaux, A., Gurol-Urganci, I., Harris, Tina, Hawdon, J., Heighway, E., Karia, A., Khalil, A., Muller, P., Thomas, L., Waite, L., Webster, K., and van der Meulen, J.

Subjects
National audit, audit, maternity, perinatal
Abstract

Executive summary Introduction Maternity and perinatal services in the UK are currently subject to a number of maternity and neonatal review programmes, including quality monitoring and improvement initiatives. These programmes focus attention on the quality of care provided by maternity services in the UK at both a national level and the individual trust or board level.1–3 In parallel to the improvement initiatives for clinical care, there are ongoing improvements in the collation and processing of maternity and neonatal data, including improved capture of detailed information about demographics of birthing people and care episodes occurring along the maternity continuum of care. These data are critical to enable evaluation and implementation of improvement strategies. The National Maternity and Perinatal Audit (NMPA) uses these data to produce information that can support the improvement of maternity and perinatal care. In this report, for the first time, the NMPA is using a new centralised data source (MSDS v1.5) for births in England, while continuing to use the established centralised maternity datasets in Scotland and Wales. This report presents measures of maternity and perinatal care based on births in English, Scottish and Welsh NHS services between 1 April 2017 and 31 March 2018. The report also provides contextual information describing the characteristics of women and babies cared for during this time period and whose data have been included in this report. The limitations of MSDS mean that for births in England the key findings and recommendations made in this report are specific to data quality only. There are insufficient data to draw clinical conclusions. For births in Scotland and Wales, the consistency of the data sources used means that clinical key findings are possible in this report. However, clinical recommendations are avoided for all countries in this report. This is because the NMPA’s next clinical report for births in 2018/19 is expected to be published in early 2022 and will use MSDS data with improved completeness; as a result, it will be able to provide a more comprehensive picture of variation of care across the three countries. Throughout this document we use the term ‘birthing people’ as well as ‘women’. It is important to acknowledge that it is not only people who identify as women who access maternity and gynaecology services. Methods The analysis in this report is based on 304 518 births in NHS maternity services in England, Scotland and Wales between 1 April 2017 and 31 March 2018.* The report is estimated to have captured 41.5% of eligible births in this time period (34% of births in England, 97% of births in Wales and 100% of births in Scotland). The NMPA makes use of data collected electronically through healthcare information systems and national datasets. Data for births in England are provided by NHS Digital’s Maternity Services Data Set version 1.5 (MSDS v1.5) as well as by Hospital Episode Statistics (HES) records. * The time lag between the period covered by this report and its publication is due to the delayed receipt of the MSDS dataset for England. National Maternity and Perinatal Audit: Clinical Report 2021 xi Data for births in Scotland are provided by Public Health Scotland Data and Intelligence (formerly the Information Services Division, ISD), based on data from the Scottish Birth Record and Scottish Morbidity Records (SMR-01 and SMR-02). Linkages to records from the National Records of Scotland (NRS) are also made for births, deaths and stillbirths. Data for births in Wales are provided by the Maternity Indicators dataset (MIds), a dataset managed by the NHS Wales Informatics Service (NWIS), as well as Admitted Patient Care (APC) records from the Patient Episode Database for Wales (PEDW), and some fields from the National Community Child Health Database (NCCHD). In order to compare like with like, the majority of measures are restricted to singleton term births. As a general principle, the denominator for each measure is restricted to women or babies to whom the outcome or intervention of interest is applicable; for example, third or fourth degree tears are only measured among women who have experienced a vaginal birth. Rates of measures are also adjusted for risk factors that are beyond the control of the maternity service, such as age, parity, previous caesarean birth and clinical risk factors that may explain variation in results between organisations. The NHS trusts and boards included in the audit provided intrapartum maternity care at one or more sites. Where possible, site-level results are available on the NMPA website.

Published
2021

23. Integrated genomic analyses of ovarian carcinoma

Author

Bell, D., Berchuck, A., Birrer, M., Chien, J., Cramer, D. W., Dao, F., Dhir, R., DiSaia, P., Gabra, H., Glenn, P., Godwin, A. K., Gross, J., Hartmann, L., Huang, M., Huntsman, D. G., Iacocca, M., Imielinski, M., Kalloger, S., Karlan, B. Y., Morrison, C., Mutch, D., Olvera, N., Orsulic, S., Park, K., Petrelli, N., Rabeno, B., Rader, J. S., Sikic, B. I., Smith-McCune, K., Sood, A. K., Bowtell, D., Testa, J. R., Chang, K., Dinh, H. H., Drummond, J. A., Fowler, G., Gunaratne, P., Hawes, A. C., Kovar, C. L., Lewis, L. R., Morgan, M. B., Newsham, I. F., Santibanez, J., Reid, J. G., Trevino, L. R., Wu, Y.-Q., Wang, M., Muzny, D. M., Wheeler, D. A., Gibbs, R. A., Sivachenko, A. Y., Sougnez, C., Wilkinson, J., Bloom, T., Fennell, T., Baldwin, J., Gabriel, S., Lander, E. S., Ding, L., Fulton, R. S., Koboldt, D. C., McLellan, M. D., Wylie, T., Walker, J., O’Laughlin, M., Dooling, D. J., Fulton, L., Abbott, R., Dees, N. D., Zhang, Q., Kandoth, C., Wendl, M., Schierding, W., Shen, D., Harris, C. C., Schmidt, H., Kalicki, J., Delehaunty, K. D., Fronick, C. C., Demeter, R., Cook, L., Wallis, J. W., Lin, L., Magrini, V. J., Hodges, J. S., Eldred, J. M., Smith, S. M., Pohl, C. S., Vandin, F., Raphael, B. J., Weinstock, G. M., Mardis, E. R., Wilson, R. K., Meyerson, M., Winckler, W., Verhaak, R. G. W., Carter, S. L., Mermel, C. H., Nguyen, H., Onofrio, R. C., Hubbard, D., Gupta, S., Crenshaw, A., Ramos, A. H., Protopopov, A., Zhang, Juinhua, Kim, T. M., Perna, I., Xiao, Y., Ren, G., Sathiamoorthy, N., Lee, E., Park, P. J., Kucherlapati, R., Absher, D. M., Waite, L., Sherlock, G., Brooks, J. D., Li, J. Z., Xu, J., Myers, R. M., Laird, P. W., Cope, L., Herman, J. G., Shen, H., Weisenberger, D. J., Noushmehr, H., Pan, F., Triche, T., Jr, Berman, B. P., Van Den Berg, D. J., Buckley, J., Baylin, S. B., Jakkula, L. R., Dorton, S., Marr, H., Choi, Y. G., Wang, V., Wang, N. J., Ngai, J., Conboy, J. G., Feiler, H. S., Socci, N. D., Liang, Y., Lash, A. E., Brennan, C., Viale, A., Meng, S., Shi, Y., Li, L., Turman, Y. J., Zang, D., Helms, E. B., Zhou, X., Wu, J., Topal, M. D., Zhang, Junihua, Wu, C. J., Shukla, S., Sivachenko, A., Jing, R., Liu, Y., Noble, M., Carter, H., Kim, D., Karchin, R., Korkola, J. E., Heiser, L. M., Cho, R. J., Hu, Z., Parvin, B., Cerami, E., Olshen, A., Reva, B., Antipin, Y., Shen, R., Mankoo, P., Sheridan, R., Ciriello, G., Chang, W. K., Bernanke, J. A., Haussler, D., Benz, C. C., Stuart, J. M., Benz, S. C., Sanborn, J. Z., Vaske, C. J., Zhu, J., Szeto, C., Scott, G. K., Yau, C., Wilkerson, M. D., Zhang, N., Akbani, R., Baggerly, K. A., Yung, W. K., Weinstein, J. N., Shelton, T., Grimm, D., Hatfield, M., Morris, S., Yena, P., Rhodes, P., Sherman, M., Paulauskis, J., Millis, S., Kahn, A., Greene, J. M., Sfeir, R., Jensen, M. A., Chen, J., Whitmore, J., Alonso, S., Jordan, J., Chu, A., Zhang, Jinghui, Barker, A., Compton, C., Eley, G., Ferguson, M., Fielding, P., Gerhard, D. S., Myles, R., Schaefer, C., Mills Shaw, K. R., Vaught, J., Vockley, J. B., Good, P. J., Guyer, M. S., Ozenberger, B., Peterson, J., and Thomson, E.

Published
2011
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29. Community-dwelling men with dementia are at high risk of hip but not any other fracture: The Concord Health and Ageing in Men Project

Author

Hsu, B, Bleicher, K, Waite, L, Naganathan, V, Blyth, F, Handelsman, D, Le Couteur, D, Seibel, M, and Cumming, R

Subjects
111799 - Public Health and Health Services not elsewhere classified [FoR], mental disorders
Abstract

Aim The aim of the present longitudinal study of community‐dwelling older men was to examine the association between cognitive status at baseline, and falls, fractures and bone loss over time. Methods In the Concord Health and Aging in Men Project, 1705 community‐dwelling men aged 70–97 years had detailed baseline clinical assessment of cognitive status (dementia, mild cognitive impairment [MCI] and normal cognition), as well as depression, physical activity, neuromuscular function, health status, sociodemographics, comorbidities, medication use and serum 25 hydroxyvitamin D, 1,25 dihydroxyvitamin D and parathyroid hormone levels. During a mean follow‐up period of 6 years, participants were contacted 4‐monthly to ascertain incident falls and fractures, the latter being confirmed by radiographic reports. Bone mineral density was measured by dual X‐ray absorptiometry at multiple time‐points. Results At baseline, 120 men were assessed to have MCI and 93 men to have dementia. Over time, there were 162 first incident fractures, including 43 hip and 32 vertebral fractures. In univariate models, baseline dementia, but not MCI, predicted an increased incidence of hip fracture (HR 6.95, 95% CI 3.47–13.96), but not vertebral (HR 2.26, 95% CI 0.79–6.46) or non‐hip non‐vertebral fracture (HR 0.73, 95% CI 0.27–1.99). The strong risk of hip fractures associated with dementia remained after accounting for potential confounders (HR 4.44, 95% CI 1.97–9.98). In multivariate analyses, dementia (incidence rate ratio 2.26, 95% CI 1.70–2.99), but not MCI, was associated with an increased risk of falls compared with normal cognition. There was no association between baseline dementia and change in bone mineral density. Conclusions Older men with dementia, but not MCI, have a greater tendency to fall and sustain hip fractures, but not any other types of fractures. NHMRC, Ageing and Alzheimer's Institute, Sydney Medical School Foundation

Published
2018

34. Natural history of non-neurogenic overactive bladder and urinary incontinence over five years in community-dwelling older men: the Concord Health and Ageing in Men Project

Author

Noguchi, N, Chan, L, Cumming, R, Blyth, F, Handelsman, D, Waite, L, Le Couteur, D, and Naganathan, V

Subjects
public health, urologic and male genital diseases, female genital diseases and pregnancy complications
Abstract

Aims To describe the natural history of non‐neurogenic overactive bladder (OAB) and urgency incontinence in community‐dwelling older men. Methods A representative sample of 1,705 community‐dwelling men aged 70 and older in a defined geographic area of Sydney, Australia, had their urinary symptoms assessed using the International Prostate Symptom Scores (IPSS) and the International Consultation of Incontinence Questionnaire (ICIQ) at baseline, 2‐year follow‐up, and 5‐year follow‐up. Four hundred and eighty‐eight men without neurological diseases or prostate cancer during follow‐up, or history of urological treatment at baseline were included in the analysis. Urgency incontinence was defined as leakage of urine occurring more than weekly in the above‐defined population. OAB was defined as either urgency or urgency incontinence according to 2002 International Continence Society consensus. Results Of the men with OAB at baseline, 29% received treatment for OAB or benign prostatic enlargement over 5 years. Of the remaining men, 33% had sustained remission at 2‐year and 5‐year follow‐ups without treatment. Of the men with OAB at 2‐year follow‐up, remission rate at 5‐year follow‐up was 53% in men without OAB at baseline and 27% in men with OAB at baseline (P = 0.23). No statistically significant difference was found in baseline characteristics between men with sustained remission and men with persistent symptoms. Conclusions One in three older men with non‐neurogenic OAB had sustained remission of symptoms without medical or surgical interventions. No significant predictor of sustained remission was identified. NHMRC Ageing and Alzheimer's Institute Sydney Medical School Foundation

Published
2017

35. Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

Author

Hinney, A., Kesselmeier, M., Huckins, Laura M, Hauser, Joanna, Karhunen, Leila, Meulenbelt, Ingrid, Slagboom, P Eline, Tortorella, Alfonso, Maj, Mario, Dedoussis, George, Dikeos, Dimitris, Gonidakis, Fragiskos, Tziouvas, Konstantinos, Southam, Lorraine, Tsitsika, Artemis, Papezova, Hana, Slachtova, Lenka, Martaskova, Debora, Kennedy, James L, Levitan, Robert D, Yilmaz, Zeynep, Huemer, Julia, Koubek, Doris, Merl, Elisabeth, Rayner, N William, Wagner, Gudrun, Lichtenstein, Paul, Breen, Gerome, Cohen-Woods, Sarah, Farmer, Anne, McGuffin, Peter, Cichon, Sven, Giegling, Ina, Herms, Stefan, Rujescu, Dan, Tachmazidou, Ioanna, Schreiber, Stefan, Wichmann, H-Erich, Dina, Christian, Sladek, Rob, Gambaro, Giovanni, Soranzo, Nicole, Julia, Antonio, Marsal, Sara, Rabionet, Raquel, Gaborieau, Valerie, Klump, Kelly L, Dick, Danielle M, Palotie, Aarno, Ripatti, Samuli, Widén, Elisabeth, Andreassen, Ole A, Espeseth, Thomas, Lundervold, Astri, Reinvang, Ivar, Steen, Vidar M, Hellard, Stephanie Le, Treasure, Janet, Mattingsdal, Morten, Ntalla, Ioanna, Bencko, Vladimir, Foretova, Lenka, Janout, Vladimir, Navratilova, Marie, Gallinger, Steven, Pinto, Dalila, Scherer, Stephen W, Aschauer, Harald, Lewis, Cathryn M, Carlberg, Laura, Schosser, Alexandra, Alfredsson, Lars, Ding, Bo, Klareskog, Lars, Padyukov, Leonid, Finan, Chris, Kalsi, Gursharan, Roberts, Marion, Logan, Darren W, Schmidt, Ulrike, Peltonen, Leena, Ritchie, Graham R S, Barrett, Jeff C, Estivill, Xavier, Hinney, Anke, Sullivan, Patrick F, Collier, David A, Zeggini, Eleftheria, Bulik, Cynthia M, Anderson, Carl A, Tozzi, Federica, Barrett, Jeffrey C, Floyd, James A B, Franklin, Christopher S, McGinnis, Ralph, Sambrook, Jennifer, Stephens, Jonathan, Ouwehand, Willem H, McArdle, Wendy L, iezebrink, Kirsty, Ring, Susan M, Strachan, David P, Alexander, Graeme, Conlon, Peter J, Dominiczak, Anna, Duncanson, Audrey, Hill, Adrian, Langford, Cordelia, Jall, S., Hebebrand, Johannes, Lord, Graham, Maxwell, Alexander P, Morgan, Linda, Sandford, Richard N, Sheerin, Neil, Vannberg, Frederik O, Blackburn, Hannah, Chen, Wei-Min, Edkins, Sarah, Gorwood, Philip, Gillman, Mathew, Gray, Emma, Hunt, Sarah E, Nengut-Gumuscu, Suna, Potter, Simon, Rich, Stephen S, Simpkin, Douglas, Whittaker, Pamela, Heid, I. M., Winkler, T. W., Adan, Roger A H, de Bakker, P., Bültmann, U., Geleijnse, M., Harst, P. V., Koppelman, G., Rosmalen, J. G., van Rossum, L., Smidt, H., Swertz, M. A., Stolk, R. P., Kas, Martien J H, Alizadeh, B., de Boer, R., Boezen, H. M., Bruinenberg, M., Franke, L., van der Harst, P., Hillege, H., van der Klauw, M., Navis, G., Ormel, J., Favaro, Angela, Postma, D., Rosmalen, J., Slaets, J., Snieder, H., Stolk, R., Wolffenbuttel, B., Wijmenga, C., Berg, J., Blackwood, D., Campbell, H., Santonastaso, Paolo, Cavanagh, J., Connell, J., Connor, M., Cunningham-Burley, S., Deary, I., Dominiczak, A., Ellis, P., FitzPatrick, B., Ford, I., Gertz, R., Fernández-Aranda, Fernando, Grau, A., Haddow, G., Jackson, C., Kerr, S., Lindsay, R., McGilchrist, M., McIntyre, D., Morris, A., Morton, R., Muir, W., Gratacos, Monica, Murray, G., Palmer, C., Pell, J., Philp, A., Porteous, D., Porteous, M., Procter, R., Ralston, S., Reid, D., Sinnott, R., Rybakowski, Filip, Smith, B., Clair, D. S., Sullivan, F., Sweetland, M., Ure, J., Watt, G., Wolf, R., Wright, A., Berndt, S. I., Gustafsson, S., Dmitrzak-Weglarz, Monika, Mägi, R., Ganna, A., Wheeler, E., Feitosa, M. F., Justice, A. E., Monda, K. L., Croteau- Chonka, D. C., Day, F. R., Esko, T., Fall, T., Volckmar, A-L, Kaprio, Jaakko, Ferreira, T., Gentilini, D., Jackson, A. U., Luan, J., Randall, J. C., Vedantam, S., Willer, C. J., Wood, A. R., Workalemahu, T., Keski-Rahkonen, Anna, Hu, Y. J., Lee, S. H., Liang, L., Lin, D. Y., Min, J. L., Neale, B. M., Thorleifsson, G., Yang, J., Albrecht, E., Amin, N., Raevuori-Helkamaa, Anu, Bragg-Gresham, J. L., Cadby, G., den Heijer, M., Eklund, N., Fischer, K., Goel, A., Hottenga, J. J., Huffman, J. E., Jarick, I., Johansson, A., Van Furth, Eric F, Johnson, T., Kanoni, S., Kleber, M. E., König, I. R., Kristiansson, K., Kutalik, Z., Lamina, C., Lecoeur, C., Li, G., Mangino, M., Slof-Op't Landt, Margarita C T, McArdle, W. L., Medina-Gomez, C., Müller-Nurasyid, M., Ngwa, J. S., Nolte, I. M., Paternoster, L., Pechlivanis, S., Perola, M., Peters, M. J., Preuss, M., Hudson, James I, Rose, L. M., Shi, J., Shungin, D., Smith, A. V., Strawbridge, R. J., Surakka, I., Teumer, A., Trip, M. D., Tyrer, J., Van Vliet- Ostaptchouk, J. V., Reichborn-Kjennerud, Ted, Vandenput, L., Waite, L. L., Zhao, J. H., Absher, D., Asselbergs, F. W., Atalay, M., Attwood, A. P., Balmforth, A. J., Basart, H., Beilby, J., Knudsen, Gun Peggy S, Bonnycastle, L. L., Brambilla, P., Chasman, D. I., Chines, P. S., Collins, F. S., Connell, J. M., Cookson, W., de Faire, U., Monteleone, Palmiero, de Vegt, F., Dei, M., Dimitriou, M., Edkins, S., Estrada, K., Evans, D. M., Farrall, M., Ferrario, M. M., Ferrières, J., Kaplan, Allan S, Frau, F., Gejman, P. V., Grallert, H., Grönberg, H., Gudnason, V., Hall, A. S., Hall, P., Hartikainen, A. L., Hayward, C., Heard-Costa, N. L., Föcker, M., Karwautz, Andreas, Heath, A. C., Hebebrand, J., Homuth, G., Hu, F. B., Hunt, S. E., Hyppönen, E., Iribarren, C., Jacobs, K. B., Jansson, J. O., Jula, A., Hakonarson, Hakon, Kähönen, M., Kathiresan, S., Kee, F., Khaw, K. T., Kivimaki, M., Koenig, W., Kraja, A. T., Kumari, M., Kuulasmaa, K., Kuusisto, J., Berrettini, Wade H, Laitinen, J. H., Lakka, T. A., Langenberg, C., Launer, L. J., Lind, L., Lindström, J., Liu, J., Liuzzi, A., Lokki, M. L., Lorentzon, M., Guo, Yiran, Madden, P. A., Magnusson, P. K., Manunta, P., Marek, D., März, W., Mateo Leach, I., McKnight, B., Medland, S. E., Mihailov, E., Milani, L., Li, Dong, Montgomery, G. W., Mooser, V., Mühleisen, T. W., Munroe, P. B., Musk, A. W., Narisu, N., Nicholson, G., Nohr, E. A., Ong, K. K., Schork, Nicholas J, Oostra, B. A., Palmer, C. N., Palotie, A., Peden, J. F., Pedersen, N., Peters, A., Polasek, O., Pouta, A., Pramstaller, P. P., Prokopenko, I., Komaki, Gen, Pütter, C., Radhakrishnan, A., Raitakari, O., Rendon, A., Rivadeneira, F., Rudan, I., Saaristo, T. E., Sambrook, J. G., Sanders, A. R., Sanna, S., Ando, Tetsuya, Saramies, J., Schipf, S., Schreiber, S., Schunkert, H., Shin, S. Y., Signorini, S., Sinisalo, J., Skrobek, B., Soranzo, N., Stancakova, A., Inoko, Hidetoshi, Stark, K., Stephens, J. C., Stirrups, K., Stumvoll, M., Swift, A. J., Theodoraki, E. V., Thorand, B., Tregouet, D. A., Tremoli, E., Esko, Tõnu, Van der Klauw, M. M., van Meurs, J. B., Vermeulen, S. H., Viikari, J., Virtamo, J., Vitart, V., Waeber, G., Wang, Z., Widen, E., Wild, S. H., Antel, J., Fischer, Krista, Willemsen, G., Winkelmann, B. R., Witteman, J. C., Wolffenbuttel, B. H., Wong, A., Wright, A. F., Zillikens, M., Amouyel, P., Boehm, B. O., Boerwinkle, E., Männik, Katrin, Boomsma, D. I., Caulfield, M. J., Chanock, S. J., Cupples, L., Cusi, D., Dedoussis, G. V., Erdmann, J., Eriksson, J. G., Franks, P. W., Froguel, P., Metspalu, Andres, Gieger, C., Gyllensten, U., Hamsten, A., Harris, T. B., Hengstenberg, C., Hicks, A. A., Hingorani, A., Hofman, A., Hovingh, K. G., Baker, Jessica H, Hveem, K., Illig, T., Jarvelin, M. R., Jöckel, K. H., Keinanen-Kiukaanniemi, S. M., Kiemeney, L. A., Kuh, D., Laakso, M., Lehtimäki, T., Levinson, D. F., Cone, Roger D, Martin, N. G., Metspalu, A., Morris, A. D., Nieminen, M. S., Njølstad, I., Ohlsson, C., Oldehinkel, A. J., Ouwehand, W. H., Palmer, L. J., Penninx, B., Dackor, Jennifer, Power, C., Province, M. A., Psaty, B. M., Qi, L., Rauramaa, R., Ridker, P. M., Ripatti, S., Salomaa, V., Samani, N. J., DeSocio, Janiece E, Sørensen, T. I., Spector, T. D., Stefansson, K., Tönjes, A., Tuomilehto, J., Uitterlinden, A. G., Uusitupa, M., Vollenweider, P., Wallaschofski, H., Hilliard, Christopher E, Wareham, N. J., Watkins, H., Wichmann, H, Wilson, J. F., Abecasis, G. R., Assimes, T. L., Barroso, I., Boehnke, M., Borecki, I. B., Deloukas, P., O'Toole, Julie K, Fox, C. S., Frayling, T., Groop, L. C., Haritunian, T., Hunter, D., Kaplan, R. C., Karpe, F., Moffatt, M., Mohlke, K. L., Pantel, Jacques, O'Connell, J. R., Pawitan, Y., Schadt, E. E., Schlessinger, D., Steinthorsdottir, V., Strachan, D. P., Thorsteinsdottir, U., van Duijn, C. M., Visscher, P. M., Di Blasio, A. M., Perica, Vesna Boraska, Szatkiewicz, Jin P, Hirschhorn, J. N., Lindgren, C. M., Morris, A. P., Meyre, D., Scherag, A., McCarthy, M. I., Speliotes, E. K., North, K. E., Loos, R. J., Grant, S. F. A., Taico, Chrysecolla, Adair, L. S., Ang, W., van Beijsterveldt, T., Bergen, N., Benke, K., Berry, D. J., Bradfield, J. P., Charoen, P., Zerwas, Stephanie, Coin, L., Cooper, C., Cousminer, D. L., Das, S., Davis, O. S., Elliott, P., Estivill, X., Feenstra, B., Trace, Sara E, Flexeder, C., Freathy, R. M., Gaillard, R., Geller, F., Gillman, M., Grant, S. F., Groen-Blokhuis, M., Goh, L. K., Guxens, M., Davis, Oliver S P, Hakonarson, H., Hattersley, A. T., Haworth, C. M., Hadley, D., Heinrich, J., Hocher, B., Holloway, J. W., Helder, Sietske, Holst, C., Horikoshi, M., Huikari, V., Hypponen, E., Iñiguez, C., Jaddoe, V. W., Kaakinen, M., Kilpeläinen, T. O., Bühren, Katharina, Kirin, M., Kowgier, M., Lakka, H. M., Lange, L. A., Lawlor, D. A., Lewin, A., Lindgren, C., Lindi, V., Burghardt, Roland, Maggi, R., Marsh, J., Melbye, M., Middeldorp, C., Millwood, I., Mook-Kanamori, D. O., Murray, J. C., Nivard, M., de Zwaan, Martina, Ntalla, I., Oken, E., O'Reilly, P. F., Panoutsopoulou, K., Pararajasingham, J., Pearson, E. R., Pennell, C. E., Egberts, Karin, Price, T. S., Raitakari, O. T., Rodriguez, A., Salem, R. M., Saw, S. M., Sebert, S., Siitonen, N., Ehrlich, Stefan, Simell, O., Sovio, U., Pourcain, B. S., Sunyer, J., Taal, H. R., Teo, Y. Y., Thiering, E., Tiesler, C., Herpertz-Dahlmann, Beate, Timpson, N. J., Valcárcel, B., Warrington, N. M., White, S., Widén, E., Yaghootkar, H., Zeggini, E., Herzog, Wolfgang, Elks, C. E., Perry, J. R., Sulem, P., Franceschini, N., He, C., Lunetta, K. L., Visser, J. A., Byrne, E. M., Imgart, Hartmut, Gudbjartsson, D. F., Koller, D. L., Lin, P., Marongiu, M., McArdle, P. F., Scherag, André, Stolk, L., van Wingerden, S. H., Corre, T., Ingelsson, E., Smith, E. N., Scherag, Susann, Ulivi, S., Warrington, M., Zgaga, L., Alavere, H., Aspelund, T., Bandinelli, S., Berenson, G. S., Bergmann, S., Zipfel, Stephan, Blackburn, H., Buring, J. E., Busonero, F., Chen, W., Cornelis, M. C., Couper, D., Coviello, A. D., Boni, Claudette, d'Adamo, P., de Geus, E. J., Döring, A., Davey Smith, G., Easton, D. F., Eiriksdottir, G., Emilsson, V., Eriksson, J., Ramoz, Nicolas, Ferrucci, L., Folsom, A. R., Foroud, T., Garcia, M., Gasparini, P., Hankinson, S. E., Versini, Audrey, Ferreli, L., Hernandez, D. G., Järvelin, M. R., Johnson, A. D., Karasik, D., Brandys, Marek K, Kiel, D. P., Kolcic, I., Kraft, P., Laven, J. S., Li, S., Levy, D., Danner, Unna N, Murray, S. S., Nalls, M. A., Navarro, P., Nelis, M., Ness, A. R., Northstone, K., de Kove, Carolien, Peacock, M., Paré, G., Parker, A. N., Pedersen, N. L., Peltonen, L., Pharoah, P., Hendriks, Judith, Plump, A. S., Porcu, E., Rafnar, T., Rice, J. P., Ring, S. M., Sala, C., Koeleman, Bobby P C, Schork, N. J., Scuteri, A., Segrè, A. V., Shuldiner, A. R., Srinivasan, S. R., Ophoff, Roel A, Tammesoo, M. L., Tikkanen, E., Toniolo, D., Tsui, K., Tryggvadottir, L., Uda, M., van Dam, R. M., Strengman, Eric, Waterworth, D. M., Weedon, M. N., Wichmann, H. E., Young, L., van Elburg, Annemarie A, Zhai, G., Zhuang, W. V., Bierut, L. J., Boyd, H. A., Crisponi, L., Demerath, E. W., Econs, M. J., Hunter, D. J., Bruson, Alice, Streeten, E. A., Clementi, Maurizio, Murabito, J. M., Murray, A., Guo, Y., Bergen, A. W., Kaye, W., Berrettini, W., Brandt, Harry, Crawford, Steve, Thornton, Laura M, Degortes, Daniela, Crow, Scott, Fichter, Manfred M, Halmi, Katherine A, Johnson, Craig, Via, Maria La, Mitchell, James, Strober, Michael, Rotondo, Alessandro, Forzan, Monica, Woodside, D Blake, Keel, Pamela, Lilenfeld, Lisa, Plotnicov, Kathy, Bergen, Andrew W, Berrettini, Wade, Kaye, Walter, Tenconi, Elena, Magistretti, Pierre, Herpertz-Dahlmann, B., de Zwaan, M., Herzog, W., Ehrlich, S., Zipfel, S., Egberts, K. M., Adan, R., Brandys, M., van Elburg, A., Docampo, Elisa, Boraska Perica, V., Franklin, C. S., Tschöp, M. H., Bulik, C. M., Collier, D., Müller, T. D., Escaramí, Geòrgia, Jiménez-Murcia, Susana, Lissowska, Jolanta, Rajewski, Andrzej, Szeszenia-Dabrowska, Neonila, Slopien, Agnieszka, Hinney, A., Kesselmeier, M., Jall, S., Volckmar, A. -L., Focker, M., Antel, J., Heid, I. M., Winkler, T. W., Grant, S. F. A., Guo, Y., Bergen, A. W., Kaye, W., Berrettini, W., Hakonarson, H., Herpertz-Dahlmann, B., De Zwaan, M., Herzog, W., Ehrlich, S., Zipfel, S., Egberts, K. M., Adan, R., Brandys, M., Van Elburg, A., Boraska Perica, V., Muller, T. D., Tschop, M. H., Zeggini, E., Bulik, C. M., Collier, D., Scherag, A., Hebebrand, J., Perica, V. B., Floyd, J. A. B., Thornton, L. M., Huckins, L. M., Southam, L., Rayner, N. W., Tachmazidou, I., Klump, K. L., Treasure, J., Lewis, C. M., Schmidt, U., Tozzi, F., Iezebrink, K., Gorwood, P., Kas, M. J. H., Favaro, A., Santonastaso, P., Fernandez-Aranda, F., Gratacos, M., Rybakowski, F., Dmitrzak-Weglarz, M., Kaprio, J., Keski-Rahkonen, A., Raevuori-Helkamaa, A., Van Furth, E. F., Slof-Op't Landt, M. C. T., Hudson, J. I., Reichborn-Kjennerud, T., Knudsen, G. P. S., Monteleone, P., Kaplan, A. S., Karwautz, A., Li, D., Komaki, G., Ando, T., Inoko, H., Esko, T., Fischer, K., Mannik, K., Metspalu, A., Baker, J. H., Cone, R. D., Dackor, J., Desocio, J. E., Hilliard, C. E., O'Toole, J. K., Pantel, J., Szatkiewicz, J. P., Taico, C., Zerwas, S., Trace, S. E., Davis, O. S. P., Helder, S., Buhren, K., Burghardt, R., Imgart, H., Scherag, S., Boni, C., Ramoz, N., Versini, A., Danner, U. N., de Kove, C., Hendriks, J., Koeleman, B. P. C., Ophoff, R. A., Strengman, E., Bruson, A., Clementi, M., Degortes, D., Forzan, M., Tenconi, E., Docampo, E., Jimenez-Murcia, G. E. S., Lissowska, J., Rajewski, A., Szeszenia-Dabrowska, N., Slopien, A., Hauser, J., Karhunen, L., Meulenbelt, I., Slagboom, P. E., Tortorella, A., Maj, M., Dedoussis, G., Dedoussis, G. V., Dikeos, D., Gonidakis, F., Tziouvas, K., Tsitsika, A., Papezova, H., Slachtova, L., Martaskova, D., Kennedy, J. L., Levitan, R. D., Yilmaz, Z., Huemer, J., Koubek, D., Merl, E., Wagner, G., Lichtenstein, P., Breen, G., Cohen-Woods, S., Farmer, A., Mcguffin, P., Cichon, S., Giegling, I., Herms, S., Rujescu, D., Schreiber, S., Wichmann, H. -E., Christian, D., Sladek, R., Gambaro, G., Soranzo, N., Julia, A., Marsal, S., Rabionet, R., Gaborieau, V., Dick, D. M., Palotie, A., Ripatti, S., Widen, E., Andreassen, O. A., Espeseth, T., Lundervold, A., Reinvang, I., Steen, V. M., Le Hellard, S., Mattingsdal, M., Ntalla, I., Bencko, V., Foretova, L., Janout, V., Navratilova, M., Gallinger, S., Pinto, D., Scherer, S. W., Aschauer, H., Carlberg, L., Schosser, A., Alfredsson, L., Ding, B., Klareskog, L., Padyukov, L., Finan, C., Kalsi, G., Roberts, M., Logan, D. W., Peltonen, L., Ritchie, G. R. S., Barrett, J. C., Estivill, X., Sullivan, P. F., Anderson, C. A., Mcginnis, R., Sambrook, J., Stephens, J., Ouwehand, W. H., Mcardle, W. L., Mcardle, P. F., Ring, S. M., Strachan, D. P., Alexander, G., Conlon, P. J., Dominiczak, A., Duncanson, A., Hill, A., Langford, C., Lord, G., Maxwell, A. P., Morgan, L., Sandford, R. N., Sheerin, N., Vannberg, F. O., Chen, W. -M., Edkins, S., Gillman, M., Gray, E., Hunt, S. E., Nengut, S. -G., Potter, S., Rich, S. S., Simpkin, D., Whittaker, P., Adair, L. S., Ang, W., Atalay, M., van Beijsterveldt, T., Bergen, N., Benke, K., Berry, D. J., Boomsma, D. I., Bradfield, J. P., Charoen, P., Coin, L., Cooper, C., Cousminer, D. L., Das, S., Elliott, P., Evans, D. M., Feenstra, B., Flexeder, C., Frayling, T., Freathy, R. M., Gaillard, R., Geller, F., Groen-Blokhuis, M., Goh, L. K., Guxens, M., Hattersley, A. T., Haworth, C. M., Hadley, D., Heinrich, J., Hirschhorn, J. N., Hocher, B., Holloway, J. W., Holst, C., Hottenga, J. J., Horikoshi, M., Huikari, V., Hypponen, E., Iniguez, C., Jaddoe, V. W., Jarvelin, M. R., Kaakinen, M., Kilpelainen, T. O., Kirin, M., Kowgier, M., Lakka, H. M., Lakka, T. A., Lange, L. A., Lawlor, D. A., Lehtimaki, T., Lewin, A., Lindgren, C., Lindi, V., Maggi, R., Marsh, J., Mccarthy, M. I., Melbye, M., Middeldorp, C., Millwood, I., Mohlke, K. L., Mook-Kanamori, D. O., Murray, J. C., Nivard, M., Nohr, E. A., Oken, E., Ong, K. K., O'Reilly, P. F., Palmer, L. J., Panoutsopoulou, K., Pararajasingham, J., Pearson, E. R., Pennell, C. E., Power, C., Price, T. S., Prokopenko, I., Raitakari, O. T., Rodriguez, A., Salem, R. M., Saw, S. M., Sebert, S., Siitonen, N., Simell, O., Sorensen, T. I., Sovio, U., Pourcain, B. S., Sunyer, J., Taal, H. R., Teo, Y. Y., Thiering, E., Tiesler, C., Timpson, N. J., Uitterlinden, A. G., Valcarcel, B., Warrington, N. M., White, S., Willemsen, G., Wilson, J. F., Yaghootkar, H., Elks, C. E., Perry, J. R., Sulem, P., Chasman, D. I., Franceschini, N., He, C., Lunetta, K. L., Visser, J. A., Byrne, E. M., Gudbjartsson, D. F., Koller, D. L., Kutalik, Z., Lin, P., Mangino, M., Marongiu, M., Smith, A. V., Stolk, L., van Wingerden, S. H., Zhao, J. H., Albrecht, E., Corre, T., Ingelsson, E., Hayward, C., Magnusson, P. K., Smith, E. N., Ulivi, S., Warrington, M., Zgaga, L., Alavere, H., Amin, N., Aspelund, T., Bandinelli, S., Barroso, I., Berenson, G. S., Bergmann, S., Boerwinkle, E., Buring, J. E., Busonero, F., Campbell, H., Chanock, S. J., Cornelis, M. C., Couper, D., Coviello, A. D., D'Adamo, P., de Faire, U., de Geus, E. J., Deloukas, P., Doring, A., Davey Smith, G., Easton, D. F., Eiriksdottir, G., Emilsson, V., Eriksson, J., Ferrucci, L., Folsom, A. R., Foroud, T., Garcia, M., Gasparini, P., Gieger, C., Gudnason, V., Hall, P., Hankinson, S. E., Ferreli, L., Heath, A. C., Hernandez, D. G., Hofman, A., Hu, F. B., Illig, T., Karasik, D., Khaw, K. T., Kiel, D. P., Kolcic, I., Kraft, P., Launer, L. J., Laven, J. S., Li, S., Liu, J., Levy, D., Martin, N. G., Mooser, V., Murray, S. S., Nalls, M. A., Navarro, P., Nelis, M., Ness, A. R., Northstone, K., Oostra, B. A., Peacock, M., Pare, G., Parker, A. N., Pedersen, N. L., Pharoah, P., Polasek, O., Plump, A. S., Pouta, A., Porcu, E., Rafnar, T., Rice, J. P., Rivadeneira, F., Rudan, I., Sala, C., Salomaa, V., Sanna, S., Schlessinger, D., Scuteri, A., Segre, A. V., Shuldiner, A. R., Srinivasan, S. R., Tammesoo, M. L., Tikkanen, E., Toniolo, D., Tsui, K., Tryggvadottir, L., Tyrer, J., Uda, M., van Dam, R. M., van Meurs, J. B., Vollenweider, P., Waeber, G., Wareham, N. J., Waterworth, D. M., Weedon, M. N., Wright, A. F., Young, L., Zhai, G., Zhuang, W. V., Bierut, L. J., Boyd, H. A., Crisponi, L., Demerath, E. W., van Duijn, C. M., Econs, M. J., Harris, T. B., Hunter, D. J., Loos, R. J., Ridker, P. M., Spector, T. D., Streeten, E. A., Stefansson, K., Thorsteinsdottir, U., Murabito, J. M., Murray, A., Brandt, H., Crawford, S., Crow, S., Fichter, M. M., Halmi, K. A., Johnson, C., La Via, M., Mitchell, J., Strober, M., Rotondo, A., Woodside, D. B., Keel, P., Lilenfeld, L., Plotnicov, K., Magistretti, P., Montgomery, G. W., Blackburn, H., Schork, N. J., Hinney, Anke, Kesselmeier, Miriam, Jall, Sigrid, Volckmar, Anna-Lena, Föcker, Manuel, Hebebrand, J, GCAN, WTCCC3, GIANT, EGG, Price Foundation Collaborative Group, Children’s Hospital of Philadelphia/Price Foundation, Cardiology, Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, ACS - Atherosclerosis & ischemic syndromes, Hinney, A, Kesselmeier, M, Jall, S, Volckmar, Al, Focker, M, Antel, J, Gcan, Wtccc3, Heid, Im, Winkler, Tw, Grant, Sfa, Giant, Manunta, P, Sfa, Grant, Egg, Guo, Y, Bergen, Aw, Kaye, W, Berrettini, W, Hakonarson, H, Price Foundation Collaborative, Group, Children’s Hospital of Philadelphia/Price, Foundation, Herpertz-Dahlmann, B, de Zwaan, M, Herzog, W, Ehrlich, S, Zipfel, S, Egberts, Km, Adan, R, Brandys, M, van Elburg, A, Perica, Vb, Franklin, C, Tschop, Mh, Zeggini, E, Bulik, Cm, Collier, D, Scherag, A, Muller, Td, Animal Ecology, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Methodology, Volckmar, A-L, Föcker, M, Gcan, Wtccc, Gasparini, P, D'Adamo, A, Children’S Hospital of Philadelphia/Price, Foundation, Boraska Perica, V, Tschöp, Mh, and Müller, Td

Subjects
Netherlands Twin Register (NTR), Male, Anorexia Nervosa, Genome-wide association study, Cardiovascular, Linkage Disequilibrium, Body Mass Index, 0302 clinical medicine, Databases, Genetic, WTCCC3, Aetiology, Cancer, 0303 health sciences, Loci, Genetic Predisposition to Disease/genetics, Cross-disorder, Anorèxia nerviosa, anorexia nervosa (AN), Shared, 3. Good health, Psychiatry and Mental health, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Human, Alleles, Body Weight, Female, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Obesity, Polymorphism, Single Nucleotide, Risk Factors, Molecular Biology, Psychiatry and Mental Health, Cellular and Molecular Neuroscience, medicine.medical_specialty, Locus (genetics), Single-nucleotide polymorphism, ta3111, Article, 03 medical and health sciences, Genetic, SDG 3 - Good Health and Well-being, Genetics, EGG, Polymorphism, Children’s Hospital of Philadelphia/Price Foundation, body mass index (BMI), genome-wide association meta-analysis (GWAMA), Prevention, ta1184, medicine.disease, 030104 developmental biology, Endocrinology, diagnostic markers, Body mass index, Genètica, 030217 neurology & neurosurgery, 0301 basic medicine, Linkage disequilibrium, GIANT, Medizin, Obesity/genetics, Overweight, Medical and Health Sciences, Oral and gastrointestinal, Anorexia Nervosa/genetics, 2.1 Biological and endogenous factors, Psychiatry, 2. Zero hunger, Allele, Eating disorder, Single Nucleotide, Biological Sciences, Polymorphism, Single Nucleotide/genetics, Price Foundation Collaborative Group, Stroke, psychiatric disorders, Gene Frequency/genetics, medicine.symptom, Databases, Internal medicine, Body Weight/genetics, medicine, Journal Article, Linkage Disequilibrium/genetics, ddc:610, Metabolic and endocrine, Nutrition, 030304 developmental biology, GCAN, business.industry, Risk Factor, Human Genome, Psychology and Cognitive Sciences, Bulimia nervosa, business
Abstract

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values

Published
2017

36. Sarcopenic Obesity and Its Temporal Associations With Changes in Bone Mineral Density, Incident Falls, and Fractures in Older Men: The Concord Health and Ageing in Men Project

Author

Scott, D, Seibel, M, Cumming, R, Naganathan, V, Blyth, F, Le Couteur, D, Handelsman, D, Waite, L, and Hirani, V

Subjects
public health
Abstract

Body composition and muscle function have important implications for falls and fractures in older adults. We aimed to investigate longitudinal associations between sarcopenic obesity and its components with bone mineral density (BMD) and incident falls and fractures in Australian community‐dwelling older men. A total of 1486 men aged ≥70 years from the Concord Health and Ageing in Men Project (CHAMP) study were assessed at baseline (2005–2007), 2‐year follow‐up (2007–2009; n = 1238), and 5‐year follow‐up (2010–2013; n = 861). At all three time points, measurements included appendicular lean mass (ALM), body fat percentage and total hip BMD, hand‐grip strength, and gait speed. Participants were contacted every 4 months for 6.1 ± 2.1 years to ascertain incident falls and fractures, the latter being confirmed by radiographic reports. Sarcopenic obesity was defined using sarcopenia algorithms of the European Working Group on Sarcopenia (EWGSOP) and the Foundation for the National Institutes of Health (FNIH) and total body fat ≥30% of total mass. Sarcopenic obese men did not have significantly different total hip BMD over 5 years compared with non‐sarcopenic non‐obese men (p > 0.05). EWGSOP‐defined sarcopenic obesity at baseline was associated with significantly higher 2‐year fall rates (incidence rate ratio [IRR] 1.66; 95% confidence interval [CI] 1.16–2.37), as were non‐sarcopenic obesity (1.30; 1.04–1.62) and sarcopenic non‐obesity (1.58; 1.14–2.17), compared with non‐sarcopenic non‐obese. No association with falls was found for sarcopenic obesity using the FNIH definition (1.01; 0.63–1.60), but after multivariable adjustment, the FNIH‐defined non‐sarcopenic obese group had a reduced hazard for any 6‐year fracture compared with sarcopenic obese men (hazard ratio 0.44; 95% CI 0.23–0.86). In older men, EWGSOP‐defined sarcopenic obesity is associated with increased fall rates over 2 years, and FNIH‐defined sarcopenic obese men have increased fracture risk over 6 years compared with non‐sarcopenic obese men. © 2016 American Society for Bone and Mineral Research. NHMRC, Ageing and Alzheimer's Institute

Published
2016

37. Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index

Author

Hoggart, C, Venturini, G, Mangino, M, Gomez, F, Ascari, G, Zhao, J, Teumer, A, Winkler, T, Tšernikova, N, Luan, J, Mihailov, E, Ehret, G, Zhang, W, Lamparter, D, Esko, T, Macé, A, Rüeger, S, Bochud, P, Barcella, M, Dauvilliers, Y, Benyamin, B, Evans, D, Hayward, C, Lopez, M, Franke, L, Russo, A, Heid, I, Salvi, E, Vendantam, S, Arking, D, Boerwinkle, E, Chambers, J, Fiorito, G, Grallert, H, Guarrera, S, Homuth, G, Huffman, J, Porteous, D, Berg, J, Blackwood, D, Campbell, H, Cavanagh, J, Connell, J, Connor, M, Cunningham Burley, S, Deary, I, Dominiczak, A, Ellis, P, Fitzpatrick, B, Ford, I, Gertz, R, Grau, A, Haddow, G, Jackson, C, Kerr, S, Lindsay, R, Mcgilchrist, M, Mcintyre, D, Morris, A, Morton, R, Muir, W, Murray, G, Palmer, C, Pell, J, Philp, A, Porteous, M, Procter, R, Ralston, S, Reid, D, Sinnott, R, Smith, B, St Clair, D, Sullivan, F, Sweetland, M, Ure, J, Watt, G, Wolf, R, Wright, A, de Bakker, P, Bültmann, U, Geleijnse, M, Harst, P, Koppelman, G, Rosmalen, J, van Rossum, L, Smidt, H, Swertz, M, Stolk, R, Alizadeh, B, de Boer, R, Boezen, H, Bruinenberg, M, van der Harst, P, Hillege, H, van der Klauw, M, Navis, G, Ormel, J, Postma, D, Slaets, J, Snieder, H, Wolffenbuttel, B, Wijmenga, C, Berndt, S, Gustafsson, S, Mägi, R, Ganna, A, Wheeler, E, Feitosa, M, Justice, A, Monda, K, Croteau Chonka, D, Day, F, Fall, T, Ferreira, T, Gentilini, D, Jackson, A, Randall, J, Vedantam, S, Willer, C, Wood, A, Workalemahu, T, Hu, Y, Lee, S, Liang, L, Lin, D, Min, J, Neale, B, Thorleifsson, G, Yang, J, Albrecht, E, Amin, N, Bragg Gresham, J, Cadby, G, den Heijer, M, Eklund, N, Fischer, K, Goel, A, Hottenga, J, Jarick, I, Johansson, A, Johnson, T, Kanoni, S, Kleber, M, König, I, Kristiansson, K, Kutalik, Z, Lamina, C, Lecoeur, C, Li, G, Mcardle, W, Medina Gomez, C, Müller Nurasyid, M, Ngwa, J, Nolte, I, Paternoster, L, Pechlivanis, S, Perola, M, Peters, M, Preuss, M, Rose, L, Shi, J, Shungin, D, Smith, A, Strawbridge, R, Surakka, I, Trip, M, Tyrer, J, Van Vliet Ostaptchouk, J, Vandenput, L, Waite, L, Absher, D, Asselbergs, F, Atalay, M, Attwood, A, Balmforth, A, Basart, H, Beilby, J, Bonnycastle, L, BRAMBILLA, PAOLO, Chasman, D, Chines, P, Collins, F, Cookson, W, de Faire, U, de Vegt, F, Dei, M, Dimitriou, M, Edkins, S, Estrada, K, Farrall, M, Ferrario, M, Ferrières, J, Frau, F, Gejman, P, Grönberg, H, Gudnason, V, Hall, A, Hall, P, Hartikainen, A, Heard Costa, N, Heath, A, Hebebrand, J, Hu, F, Hunt, S, Hyppönen, E, Iribarren, C, Jacobs, K, Jansson, J, Jula, A, Kähönen, M, Kathiresan, S, Kee, F, Khaw, K, Kivimaki, M, Koenig, W, Kraja, A, Kumari, M, Karikuulasmaa, N, Kuusisto, J, Laitinen, J, Lakka, T, Langenberg, C, Launer, L, Lind, L, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Lorentzon, M, Madden, P, Magnusson, P, Manunta, P, Marek, D, März, W, Leach, I, Mcknight, B, Medland, S, Milani, L, Montgomery, G, Mooser, V, Mühleisen, T, Munroe, P, Musk, A, Narisu, N, Nicholson, G, Nohr, E, Ong, K, Oostra, B, Palotie, A, Peden, J, Pedersen, N, Peters, A, Polasek, O, Pouta, A, Pramstaller, P, Prokopenko, I, Pütter, C, Radhakrishnan, A, Raitakari, O, Rendon, A, Rivadeneira, F, Rudan, I, Saaristo, T, Sambrook, J, Sanders, A, Sanna, S, Saramies, J, Schipf, S, Schreiber, S, Schunkert, H, Shin, S, Signorini, S, Sinisalo, J, Skrobek, B, Soranzo, N, Stancakova, A, Stark, K, Stephens, J, Stirrups, K, Stumvoll, M, Swift, A, Theodoraki, E, Thorand, B, Tregouet, D, Tremoli, E, Van der Klauw, M, van Meurs, J, Vermeulen, S, Viikari, J, Virtamo, J, Vitart, V, Waeber, G, Wang, Z, Widen, E, Wild, S, Willemsen, G, Winkelmann, B, Witteman, J, Wong, A, Zillikens, M, Amouyel, P, Boehm, B, Boomsma, D, Caulfield, M, Chanock, S, Cupples, L, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, J, Franks, P, Froguel, P, Gieger, C, Gyllensten, U, Hamsten, A, Harris, T, Hengstenberg, C, Hicks, A, Hingorani, A, Hinney, A, Hofman, A, Hovingh, K, Hveem, K, Illig, T, Jarvelin, M, Jöckel, K, Keinanen Kiukaanniemi, S, Kiemeney, L, Kuh, D, Laakso, M, Lehtimäki, T, Levinson, D, Martin, N, Metspalu, A, Nieminen, M, Njølstad, I, Ohlsson, C, Oldehinkel, A, Ouwehand, W, Palmer, L, Penninx, B, Power, C, Province, M, Psaty, B, Qi, L, Rauramaa, R, Ridker, P, Ripatti, S, Salomaa, V, Samani, N, Sørensen, T, Spector, T, Stefansson, K, Tönjes, A, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, Vollenweider, P, Wallaschofski, H, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Abecasis, G, Assimes, T, Barroso, I, Boehnke, M, Borecki, I, Deloukas, P, Fox, C, Frayling, T, Groop, L, Haritunian, T, Hunter, D, Kaplan, R, Karpe, F, Miriammoffatt, N, Mohlke, K, O'Connell, J, Pawitan, Y, Schadt, E, Schlessinger, D, Steinthorsdottir, V, Strachan, D, Thorsteinsdottir, U, van Duijn, C, Visscher, P, Di Blasio, A, Hirschhorn, J, Lindgren, C, Meyre, D, Scherag, A, Mccarthy, M, Speliotes, E, North, K, Loos, R, Ingelsson, E, Moradpour, D, Iranzo, A, Kemp, J, Lammers, G, Aubert, V, Heim, M, Peraita Adrados, R, Santamaria, J, Negro, F, Schmidt, C, Scott, R, Strauch, K, Völzke, H, Yuan, W, 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A, Winkler, Tw, Tšernikova, N, Luan, J, Mihailov, E, Ehret, Gb, Zhang, W, Lamparter, D, Esko, T, Macé, A, Rüeger, S, Bochud, Py, Barcella, M, Dauvilliers, Y, Benyamin, B, Evans, Dm, Hayward, C, Lopez, Mf, Franke, L, Russo, A, Heid, Im, Salvi, E, Vendantam, S, Arking, De, Boerwinkle, E, Chambers, Jc, Fiorito, G, Grallert, H, Guarrera, S, Homuth, G, Huffman, Je, Porteous, D, GENERATION SCOTLAND, Consortium, LIFELINES COHORT, Study, Giant, Consortium, Manunta, Paolo, Moradpour, D, Iranzo, A, Hebebrand, J, Kemp, Jp, Lammers, Gj, Aubert, V, Heim, Mh, Martin, Ng, Montgomery, Gw, PERAITA ADRADOS, R, Santamaria, J, Negro, F, Schmidt, Co, Scott, Ra, Spector, Td, Strauch, K, Völzke, H, Wareham, Nj, Yuan, W, Bell, Jt, Chakravarti, A, Kooner, J, Peters, A, Matullo, G, Wallaschofski, H, Whitfield, Jb, Paccaud, F, Vollenweider, P, Bergmann, S, Beckmann, J, Tafti, M, Hastie, Nd, Cusi, D, Bochud, M, Frayling, Tm, Metspalu, A, Jarvelin, Mr, Scherag, A, Smith, Gd, Borecki, Ib, Rousson, V, Hirschhorn, Jn, Rivolta, C, Loos, Rj, Kutalik, Z., Hoggart, C, Zhao, J, Winkler, T, Ehret, G, Bochud, P, Evans, D, Lopez, M, Heid, I, Arking, D, Chambers, J, Huffman, J, Berg, J, Blackwood, D, Campbell, H, Cavanagh, J, Connell, J, Connor, M, Cunningham Burley, S, Deary, I, Dominiczak, A, Ellis, P, Fitzpatrick, B, Ford, I, Gertz, R, Grau, A, Haddow, G, Jackson, C, Kerr, S, Lindsay, R, Mcgilchrist, M, Mcintyre, D, Morris, A, Morton, R, Muir, W, Murray, G, Palmer, C, Pell, J, Philp, A, Porteous, M, Procter, R, Ralston, S, Reid, D, Sinnott, R, Smith, B, St Clair, D, Sullivan, F, Sweetland, M, Ure, J, Watt, G, Wolf, R, Wright, A, de Bakker, P, Bültmann, U, Geleijnse, M, Harst, P, Koppelman, G, Rosmalen, J, van Rossum, L, Smidt, H, Swertz, M, Stolk, R, Alizadeh, B, de Boer, R, Boezen, H, Bruinenberg, M, van der Harst, P, Hillege, H, van der Klauw, M, Navis, G, Ormel, J, Postma, D, Slaets, J, Snieder, H, Wolffenbuttel, B, Wijmenga, C, Berndt, S, Gustafsson, S, Mägi, R, Ganna, A, Wheeler, E, Feitosa, M, Justice, A, Monda, K, Croteau Chonka, D, Day, F, Fall, T, Ferreira, T, Gentilini, D, Jackson, A, Randall, J, Vedantam, S, Willer, C, Wood, A, Workalemahu, T, Hu, Y, Lee, S, Liang, L, Lin, D, Min, J, Neale, B, Thorleifsson, G, Yang, J, Albrecht, E, Amin, N, Bragg Gresham, J, Cadby, G, den Heijer, M, Eklund, N, Fischer, K, Goel, A, Hottenga, J, Jarick, I, Johansson, A, Johnson, T, Kanoni, S, Kleber, M, König, I, Kristiansson, K, Kutalik, Z, Lamina, C, Lecoeur, C, Li, G, Mcardle, W, Medina Gomez, C, Müller Nurasyid, M, Ngwa, J, Nolte, I, Paternoster, L, Pechlivanis, S, Perola, M, Peters, M, Preuss, M, Rose, L, Shi, J, Shungin, D, Smith, A, Strawbridge, R, Surakka, I, Trip, M, Tyrer, J, Van Vliet Ostaptchouk, J, Vandenput, L, Waite, L, Absher, D, Asselbergs, F, Atalay, M, Attwood, A, Balmforth, A, Basart, H, Beilby, J, Bonnycastle, L, Brambilla, P, Chasman, D, Chines, P, Collins, F, Cookson, W, de Faire, U, de Vegt, F, Dei, M, Dimitriou, M, Edkins, S, Estrada, K, Farrall, M, Ferrario, M, Ferrières, J, Frau, F, Gejman, P, Grönberg, H, Gudnason, V, Hall, A, Hall, P, Hartikainen, A, Heard Costa, N, Heath, A, Hu, F, Hunt, S, Hyppönen, E, Iribarren, C, Jacobs, K, Jansson, J, Jula, A, Kähönen, M, Kathiresan, S, Kee, F, Khaw, K, Kivimaki, M, Koenig, W, Kraja, A, Kumari, M, Karikuulasmaa, N, Kuusisto, J, Laitinen, J, Lakka, T, Langenberg, C, Launer, L, Lind, L, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Lorentzon, M, Madden, P, Magnusson, P, Manunta, P, Marek, D, März, W, Leach, I, Mcknight, B, Medland, S, Milani, L, Montgomery, G, Mooser, V, Mühleisen, T, Munroe, P, Musk, A, Narisu, N, Nicholson, G, Nohr, E, Ong, K, Oostra, B, Palotie, A, Peden, J, Pedersen, N, Polasek, O, Pouta, A, Pramstaller, P, Prokopenko, I, Pütter, C, Radhakrishnan, A, Raitakari, O, Rendon, A, Rivadeneira, F, Rudan, I, Saaristo, T, Sambrook, J, Sanders, A, Sanna, S, Saramies, J, Schipf, S, Schreiber, S, Schunkert, H, Shin, S, Signorini, S, Sinisalo, J, Skrobek, B, Soranzo, N, Stancakova, A, Stark, K, Stephens, J, Stirrups, K, Stumvoll, M, Swift, A, Theodoraki, E, Thorand, B, Tregouet, D, Tremoli, E, Van der Klauw, M, van Meurs, J, Vermeulen, S, Viikari, J, Virtamo, J, Vitart, V, Waeber, G, Wang, Z, Widen, E, Wild, S, Willemsen, G, Winkelmann, B, Witteman, J, Wong, A, Zillikens, M, Amouyel, P, Boehm, B, Boomsma, D, Caulfield, M, Chanock, S, Cupples, L, Dedoussis, G, Erdmann, J, Eriksson, J, Franks, P, Froguel, P, Gieger, C, Gyllensten, U, Hamsten, A, Harris, T, Hengstenberg, C, Hicks, A, Hingorani, A, Hinney, A, Hofman, A, Hovingh, K, Hveem, K, Illig, T, Jarvelin, M, Jöckel, K, Keinanen Kiukaanniemi, S, Kiemeney, L, Kuh, D, Laakso, M, Lehtimäki, T, Levinson, D, Martin, N, Nieminen, M, Njølstad, I, Ohlsson, C, Oldehinkel, A, Ouwehand, W, Palmer, L, Penninx, B, Power, C, Province, M, Psaty, B, Qi, L, Rauramaa, R, Ridker, P, Ripatti, S, Salomaa, V, Samani, N, Sørensen, T, Spector, T, Stefansson, K, Tönjes, A, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Abecasis, G, Assimes, T, Barroso, I, Boehnke, M, Borecki, I, Deloukas, P, Fox, C, Frayling, T, Groop, L, Haritunian, T, Hunter, D, Kaplan, R, Karpe, F, Miriammoffatt, N, Mohlke, K, O'Connell, J, Pawitan, Y, Schadt, E, Schlessinger, D, Steinthorsdottir, V, Strachan, D, Thorsteinsdottir, U, van Duijn, C, Visscher, P, Di Blasio, A, Hirschhorn, J, Lindgren, C, Meyre, D, Mccarthy, M, Speliotes, E, North, K, Loos, R, Ingelsson, E, Kemp, J, Lammers, G, Heim, M, Peraita Adrados, R, Schmidt, C, Scott, R, Bell, J, Whitfield, J, Hastie, N, and Da Smith, G

Subjects
Epigenomics, Male, Netherlands Twin Register (NTR), body mass index, gene, SNP, Cancer Research, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Potassium Channels, Glucose Transport Proteins, Facilitative, Medizin, Genome-wide association study, CHILDREN, ddc:616.07, FAMILIES, Body Mass Index, 0302 clinical medicine, Polymorphism (computer science), Genotype, LifeLines Cohort study, GENETICS & HEREDITY, Tandem Pore Domain, Genetics (clinical), ASSOCIATIONS, ddc:616, Genetics, 0303 health sciences, QUANTITATIVE TRAIT LOCI, Ecology, Genomics, Single Nucleotide, Generation Scotland Consortium, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], OBESITY, Physical Sciences, KCNK9 protein, Epigenetics, Female, ALCOHOLISM, Glucose Transport Proteins, Life Sciences & Biomedicine, Statistics (Mathematics), Human, Research Article, VARIANCES, Adult, PENETRANCE, GENES, lcsh:QH426-470, Evolution, European Continental Ancestry Group, Single-nucleotide polymorphism, Biostatistics, Biology, Quantitative trait locus, Polymorphism, Single Nucleotide, White People, 03 medical and health sciences, Genomic Imprinting, Potassium Channels, Tandem Pore Domain, Genetic, Behavior and Systematics, SDG 3 - Good Health and Well-being, Genetic linkage, GIANT Consortium, Genome-Wide Association Studies, Humans, Genetic Predisposition to Disease, Statistical Methods, Allele, Polymorphism, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Gene Expression Regulation, Genome-Wide Association Study, Obesity, 030304 developmental biology, 0604 Genetics, Science & Technology, LINKAGE ANALYSIS, SLC2A10 protein, Biology and Life Sciences, Computational Biology, Facilitative, Genome Analysis, Ecology, Evolution, Behavior and Systematic, lcsh:Genetics, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], 3111 Biomedicine, Genomic imprinting, Mathematics, 030217 neurology & neurosurgery, Developmental Biology
Abstract

The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ∼4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta = 0.11 (SD), P, Author Summary Large genetic association studies have revealed many genetic factors influencing common traits, such as body mass index (BMI). These studies assume that the effect of genetic variants is the same regardless of whether they are inherited from the mother or the father. In our study, we have developed a new approach that allows us to investigate variants whose impact depends on their parental origin (parent-of-origin effects), in unrelated samples when the parental origin cannot be inferred. This is feasible because at genetic markers at which such effects occur there is increased variability of the trait among individuals who inherited different genetic codes from their mother and their father compared to individuals who inherited the same genetic code from both parents. We applied this methodology to discover genetic markers with parent-of-origin effects (POEs) on BMI. This resulted in six candidate markers showing strong POE association. We then attempted to replicate the POE effects of these markers in family studies (where one can infer the parental origin of the inherited variants). Two of our candidates showed significant association in the family studies, the paternal and maternal effects of these markers were in the opposite direction.

Published
2014

38. Progressive Temporal Change in Serum SHBG, But Not in Serum Testosterone or Estradiol, Is Associated With Bone Loss and Incident Fractures in Older Men: The Concord Health and Ageing in Men Project

Author

Hsu, B, Seibel, M, Cumming, R, Blyth, F, Naganathan, V, Bleicher, K, Le Couteur, D, Waite, L, and Handelsman, D

Subjects
public health
Abstract

This study aimed to examine progressive temporal relationships between changes in major reproductive hormones across three waves of a cohort study of older men and (1) changes in bone mineral density (BMD) and (2) incident fractures (any, hip or non‐vertebral) over an average of 6 years of follow‐up. The CHAMP cohort of men aged 70 years and older were assessed at baseline (2005 to 2007, n = 1705), 2‐year follow‐up (n = 1367), and 5‐year follow‐up (n = 958). Serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) (by liquid chromatography–tandem mass spectrometry [LC‐MS/MS]), and sex hormone–binding globulin (SHBG), luteinizing hormone (LH), and follicle‐stimulating hormone (FSH) (by immunoassay) were measured at all time‐points, whereas free testosterone (cFT) was calculated using a well‐validated formula. Hip BMD was measured by dual‐energy X‐ray absorptiometry (DXA) at all three time‐points, and fracture data were verified radiographically. Statistical modeling was done using general estimating equations (GEEs). For total hip BMD, univariable analyses revealed inverse associations with temporal changes in serum SHBG, FSH, and LH and positive associations for serum E1 and cFT across the three time‐points. In models adjusted for multiple covariables, serum SHBG (β = –0.029), FSH (β = –0.065), LH (β = –0.049), E1 (β = 0.019), and cFT (β = 0.033) remained significantly associated with hip BMD. However for femoral neck BMD, only FSH (β = –0.048) and LH (β = –0.036) remained associated in multivariable‐adjusted models. Temporal change in serum SHBG, but not T, E2, or other hormonal variables, was significantly associated with any, nonvertebral or hip fracture incidence in univariable analyses. In multivariable‐adjusted models, temporal increase in serum SHBG over time remained associated with any fracture (β = 0.060) and hip fracture (β = 0.041) incidence, but not nonvertebral fracture incidence. These data indicate that a progressive increase in circulating SHBG over time predicts bone loss and fracture risk in older men. Further studies are warranted to further characterize changes in circulating SHBG as a mechanism and/or biomarker of bone health during male ageing. © 2016 American Society for Bone and Mineral Research. NHMRC, Sydney Medical School Foundation, Ageing and Alzheimer's Institute

Published
2016

41. Oral health behaviours of older Australian men: the Concord Health and Ageing in Men Project.

Author

Tran, J, Wright, FAC, Takara, S, Shu, C‐C, Chu, SK‐Y, Naganathan, V, Hirani, V, Blyth, FM, Le Couteur, DG, Waite, LM, Handelsman, DJ, Seibel, MJ, Milledge, KL, Cumming, RG, Shu, C-C, Chu, Sk-Y, Blyth, F M, Le Couteur, D G, Waite, L M, and Handelsman, D J

Subjects
OLDER men, NUTRITION & oral health, MEN'S health, DENTAL floss, ORAL hygiene, DENTAL care utilization
Abstract

Background: The Concord Health and Ageing in Men Project (CHAMP) is a cohort study of the health of a representative sample of older Australian men. The aim of this paper is to describe the oral health behaviours and dental service use of CHAMP participants and explore associations between oral health behaviours with and general health status.Method: Information collected related to socio-demographics, general health, oral health service-use and oral health behaviours. Key general health conditions were ascertained from the health questionnaire and included physical capacity and cognitive status.Results: Fifty-seven percent of the men reported visiting a dental provider at least once or more a year and 56.7% did so for a "dental check-up". Of those with some natural teeth, 59.3% claimed to brush their teeth at least twice or more a day. Most men (96%) used a standard fluoride toothpaste. Few participants used dental floss, tooth picks or mouth-rinses to supplement oral hygiene. Cognitive status and self-rated general health were associated with dental visiting patterns and toothbrushing behaviour.Conclusions: Most older men in CHAMP perform favourable oral health behaviours. Smoking behaviour is associated with less favourable dental visiting patterns, and cognitive status with toothbrushing behaviour. [ABSTRACT FROM AUTHOR]

Published
2019
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42. Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders

Author

den Hoed, M, Eijgelsheim, M, Esko, T, Brundel, Bj, Peal, Ds, Evans, Dm, Nolte, Im, Segrè, Av, Holm, H, Handsaker, Re, Westra, Hj, Johnson, T, Isaacs, A, Yang, J, Lundby, A, Zhao, Jh, Kim, Yj, Go, Mj, Almgren, P, Bochud, M, Boucher, G, Cornelis, Mc, Gudbjartsson, D, Hadley, D, van der Harst, P, Hayward, C, den Heijer, M, Igl, W, Jackson, Au, Kutalik, Z, Luan, J, Kemp, Jp, Kristiansson, K, Ladenvall, C, Lorentzon, M, Montasser, Me, Njajou, Ot, O'Reilly, Pf, Padmanabhan, S, St Pourcain, B, Rankinen, T, Salo, P, Tanaka, T, Timpson, Nj, Vitart, V, Waite, L, Wheeler, W, Zhang, W, Draisma, Hh, Feitosa, Mf, Kerr, Kf, Lind, Pa, Mihailov, E, Onland Moret NC, Song, C, Weedon, Mn, Xie, W, Yengo, L, Absher, D, Albert, Cm, Alonso, A, Arking, De, de Bakker PI, Balkau, B, Barlassina, C, Benaglio, P, Bis, Jc, Bouatia Naji, N, Brage, S, Chanock, Sj, Chines, Ps, Chung, M, Darbar, D, Dina, C, Dörr, M, Elliott, P, Felix, Sb, Fischer, K, Fuchsberger, C, de Geus EJ, Goyette, P, Gudnason, V, Harris, Tb, Hartikainen, Al, Havulinna, As, Heckbert, Sr, Hicks, Aa, Hofman, A, Holewijn, S, Hoogstra Berends, F, Hottenga, Jj, Jensen, Mk, Johansson, A, Junttila, J, Kääb, S, Kanon, B, Ketkar, S, Khaw, Kt, Knowles, Jw, Kooner, As, Kors, Ja, Kumari, M, Milani, L, Laiho, P, Lakatta, Eg, Langenberg, C, Leusink, M, Liu, Y, Luben, Rn, Lunetta, Kl, Lynch, Sn, Markus, Mr, Marques Vidal, P, Mateo Leach, I, Mcardle, Wl, Mccarroll, Sa, Medland, Se, Miller, Ka, Montgomery, Gw, Morrison, Ac, Müller Nurasyid, M, Navarro, P, Nelis, M, O'Connell, Jr, O'Donnell, Cj, Ong, Kk, Newman, Ab, Peters, A, Polasek, O, Pouta, A, Pramstaller, Pp, Psaty, Bm, Rao, Dc, Ring, Sm, Rossin, Ej, Rudan, D, Sanna, S, Scott, Ra, Sehmi, Js, Sharp, S, Shin, Jt, Singleton, Ab, Smith, Av, Soranzo, N, Spector, Td, Stewart, C, Stringham, Hm, Tarasov, Kv, Uitterlinden, Ag, Vandenput, L, Hwang, Sj, Whitfield, Jb, Wijmenga, C, Wild, Sh, Willemsen, G, Wilson, Jf, Witteman, Jc, Wong, A, Wong, Q, Jamshidi, Y, Zitting, P, Boer, Jm, Boomsma, Di, Borecki, Ib, van Duijn CM, Ekelund, U, Forouhi, Ng, Froguel, P, Hingorani, A, Ingelsson, E, Kivimaki, M, Kronmal, Ra, Kuh, D, Lind, L, Martin, Ng, Oostra, Ba, Pedersen, Nl, Quertermous, T, Rotter, Ji, van der Schouw YT, Verschuren, Wm, Walker, M, Albanes, D, Arnar, Do, Assimes, Tl, Bandinelli, S, Boehnke, M, de Boer RA, Bouchard, C, Caulfield, Wl, Chambers, Jc, Curhan, G, Cusi, D, Eriksson, J, Ferrucci, L, van Gilst WH, Glorioso, N, de Graaf, J, Groop, L, Gyllensten, U, Hsueh, Wc, Hu, Fb, Huikuri, Hv, Hunter, Dj, Iribarren, C, Isomaa, B, Jarvelin, Mr, Jula, A, Kähönen, M, Kiemeney, La, van der Klauw MM, Kooner, Js, Kraft, P, Iacoviello, Licia, Lehtimäki, T, Lokki, Ml, Mitchell, Bd, Navis, G, Nieminen, Ms, Ohlsson, C, Poulter, Nr, Qi, L, Raitakari, Ot, Rimm, Eb, Rioux, Jd, Rizzi, F, Rudan, I, Salomaa, V, Sever, Ps, Shields, Dc, Shuldiner, Ar, Sinisalo, J, Stanton, Av, Stolk, Rp, Strachan, Dp, Tardif, Jc, Thorsteinsdottir, U, Tuomilehto, J, van Veldhuisen DJ, Virtamo, J, Viikari, J, Vollenweider, P, Waeber, G, Widen, E, Cho, Ys, Olsen, Jv, Visscher, Pm, Willer, C, Franke, L, Global BPgen Consortium, Cardiogram, Consortium, Erdmann, J, Thompson, Jr, PR GWAS Consortium, Pfeufer, A, QRS GWAS Consortium, Sotoodehnia, N, QT IGC Consortium, Newton Cheh, C, CHARGE AF Consortium, Ellinor, Pt, Stricker, Bh, Metspalu, A, Perola, M, Beckmann, Js, Smith, Gd, Stefansson, K, Wareham, Nj, Munroe, Pb, Sibon, Oc, Milan, Dj, Snieder, H, Samani, Nj, Loos, R. J., Global BPgen Consortium, CARDIoGRAM Consortium, PR GWAS Consortium, QRS GWAS Consortium, QT-IGC Consortium, CHARGE-AF Consortium, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Neuroscience Campus Amsterdam - Brain Imaging Technology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Humane Biologie, Epidemiology, Public Health, Clinical Genetics, Surgery, Medical Informatics, Internal Medicine, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, ICaR - Circulation and metabolism, EMGO - Lifestyle, overweight and diabetes, NCA - Brain imaging technology, ACS - Heart failure & arrhythmias, Physiology, Internal medicine, Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Molecular Neuroscience and Ageing Research (MOLAR), and Stem Cell Aging Leukemia and Lymphoma (SALL)

Subjects
Netherlands Twin Register (NTR), Aetiology, screening and detection [ONCOL 5], 030204 cardiovascular system & hematology, Arrhythmias, DISEASE, Sudden cardiac death, PR INTERVAL, 0302 clinical medicine, Gene Frequency, Heart Rate, Arrhythmias, Cardiac/genetics, 0303 health sciences, COMMON VARIANTS, Dilated cardiomyopathy, Atrial fibrillation, Single Nucleotide, Heart Rate/genetics, 3. Good health, DROSOPHILA, LIBRARY, Cardiology, QRS DURATION, Electrical conduction system of the heart, Metabolic Networks and Pathways, rhytm, conduction, gene, medicine.medical_specialty, SUSCEPTIBILITY LOCI, Quantitative Trait Loci, Cardiac/genetics, Biology, Polymorphism, Single Nucleotide, Article, Sick sinus syndrome, Heart Conduction System/physiopathology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Heart Conduction System, Internal medicine, Cardiac conduction, Heart rate, Genetics, medicine, Animals, Humans, GENOME-WIDE ASSOCIATION, Polymorphism, Health aging / healthy living Cardiovascular diseases [IGMD 5], Molecular epidemiology Aetiology, screening and detection [NCEBP 1], 030304 developmental biology, QT INTERVAL, Arrhythmias, Cardiac, ta3121, medicine.disease, Endocrinology, Genetic Loci, Heart failure, ATRIAL-FIBRILLATION, Genome-Wide Association Study
Abstract

Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets. © 2013 Nature America, Inc. All rights reserved.

Published
2013

43. Oral health of community-dwelling older Australian men: the Concord Health and Ageing in Men Project (CHAMP).

Author

Wright, F. A. C., Chu, SK‐Y, Milledge, K. L., Valdez, E., Law, G., Hsu, B., Naganathan, V., Hirani, V., Blyth, F. M., Le Couteur, D. G., Harford, J., Waite, L. M., Handelsman, D. J., Seibel, M. J., Cumming, R. G., Wright, Fac, and Chu, Sk-Y

Subjects
GERIATRIC dentistry, MEDICAL care for older people, DENTAL therapeutics, COMPLICATIONS of prosthesis, DENTAL care, PUBLIC health
Abstract

Background: The Concord Health and Ageing in Men Project (CHAMP) is a cohort study of the health of a representative sample of Australian men aged 70 years and older. The aim of this report is to describe the oral health of these men.Methods: Oral health was assessed when the men were all aged 78 years or older. Two calibrated examiners conducted a standardized intraoral assessment. Descriptive data were analysed by statistical association tests. Participants were excluded from the collection of some periodontal assessments if they had a medical contraindication.Results: Dental assessments of 614 participants revealed 90 (14.6%) were edentate. Men had a mean of 13.8 missing teeth and 10.3 filled teeth. Dentate participants had a mean of 1.1 teeth with active coronal decay. Those in the low-income group had a higher rate of decayed teeth and lower rate of filled teeth. Thirty-four participants (5.5%) had one or more dental implants, and 66.3% relied on substitute natural teeth for functional occlusion. Of those with full periodontal assessments; 90.9% had sites with pocket depths of 3 mm or more, 96.6% had sites with CAL of 5 mm or more, and 79.7% had three or more sites with GI scores of 2 or more.Conclusions: There was a high prevalence of periodontal diseases and restorative burden of dentitions, which suggests that greater attention needs to be given to prevention and health maintenance in older Australian men. [ABSTRACT FROM AUTHOR]

Published
2018
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45. Integrated genomic analyses of ovarian carcinoma

Author

Bell, D, Berchuck, A, Birrer, M, Chien, J, Cramer, DW, Dao, F, Dhir, R, DiSaia, P, Gabra, H, Glenn, P, Godwin, AK, Triche, T, Berman, BP, Van den Berg, DJ, Buckley, J, Baylin, SB, Zhang, J, Spellman, PT, Purdom, E, Iacocca, M, Shelton, T, Voet, D, Neuvial, P, Bengtsson, H, Jakkula, LR, Durinck, S, Han, J, Dorton, S, Marr, H, Zhang, H, Choi, YG, Wang, V, Wilkinson, J, Nguyen, H, Wang, NJ, Imielinski, M, Ngai, J, Conboy, JG, Parvin, B, Feiler, HS, Speed, TP, Gray, JW, Wu, CJ, Bloom, T, Levine, DA, Li, L, Socci, ND, Liang, Y, Taylor, BS, Kalloger, S, Schultz, N, Borsu, L, Lash, AE, Brennan, C, Ardlie, K, Viale, A, Shukla, S, Grimm, D, Sander, C, Ladanyi, M, Hoadley, KA, Meng, S, Du, Y, Karlan, BY, Shi, Y, Fennell, T, Cibulskis, K, Lawrence, MS, Meyerson, M, Hatfield, M, Mills, GB, Sivachenko, A, Jing, R, Park, RW, Liu, Y, Park, PJ, Ramos, AH, Noble, M, Chin, L, Carter, H, Kim, D, Morris, S, Winckler, W, Karchin, R, Morrison, C, Baldwin, J, Korkola, JE, Yena, P, Heiser, LM, Getz, G, Cho, RJ, Hu, Z, Gabriel, S, Mutch, D, Cerami, E, Rhodes, P, Olshen, A, Verhaak, RGW, Lander, ES, Reva, B, Antipin, Y, Shen, R, Olvera, N, Mankoo, P, Sheridan, R, Ciriello, G, Sherman, M, Chang, WK, Bernanke, JA, Hayes, DN, Carter, SL, Haussler, D, Orsulic, S, Benz, CC, Paulauskis, J, Stuart, JM, Zhang, N, Benz, SC, Sanborn, JZ, Vaske, CJ, Mermel, CH, Zhu, J, Szeto, C, Scott, GK, Yau, C, Rabeno, B, Ding, L, Park, K, Balu, S, Perou, CM, Saksena, G, Wilkerson, MD, Millis, S, Kahn, A, Turman, YJ, Fulton, RS, Onofrio, RC, Greene, JM, Sfeir, R, Jensen, MA, Chen, J, Whitmore, J, Alonso, S, Jordan, J, Chu, A, Rader, JS, Koboldt, DC, Zang, D, Gross, J, Barker, A, Compton, C, Eley, G, Ferguson, M, Fielding, P, Gerhard, DS, Myles, R, McLellan, MD, Schaefer, C, Helms, EB, Shaw, KRM, Sikic, BI, Vaught, J, Vockley, JB, Good, PJ, Guyer, MS, Ozenberger, B, Wylie, T, Peterson, J, Thomson, E, Smith-McCune, K, Sood, AK, Bowtell, D, Hubbard, D, Penny, R, Testa, JR, Chang, K, Walker, J, Dinh, HH, Drummond, JA, Fowler, G, Zhou, X, Gunaratne, P, Hawes, AC, Kovar, CL, Lewis, LR, Gupta, S, Morgan, MB, O'Laughlin, M, Newsham, IF, Santibanez, J, Reid, JG, Trevino, LR, Wu, J, Wu, Y-Q, Wang, M, Muzny, DM, Wheeler, DA, Gibbs, RA, Crenshaw, A, Sivachenko, AY, Topal, MD, Sougnez, C, Dooling, DJ, Fulton, L, Akbani, R, Abbott, R, Dees, ND, Zhang, Q, Kandoth, C, Wendl, M, Schierding, W, Shen, D, Harris, CC, Baggerly, KA, Schmidt, H, Wilson, RK, Kalicki, J, Delehaunty, KD, Fronick, CC, Demeter, R, Cook, L, Wallis, JW, Lin, L, Magrini, VJ, Yung, WK, Hodges, JS, Protopopov, A, Eldred, JM, Smith, SM, Pohl, CS, Vandin, F, Raphael, BJ, Weinstock, GM, Mardis, R, Kim, TM, Hartmann, L, Perna, I, Xiao, Y, Ren, G, Sathiamoorthy, N, Petrelli, N, Lee, E, Kucherlapati, R, Absher, DM, Huang, M, Waite, L, Sherlock, G, Brooks, JD, Li, JZ, Weinstein, JN, Xu, J, Myers, RM, Laird, PW, Cope, L, Herman, JG, Shen, H, Huntsman, DG, Weisenberger, DJ, Noushmehr, H, Pan, F, Massachusetts Institute of Technology. Department of Biology, Lander, Eric S., and Meyerson, Matthew L.

Subjects
endocrine system diseases, Serous carcinoma, Messenger, Gene Dosage, Cancer Genome Atlas Research Network, GYNECOLOGIC-ONCOLOGY-GROUP, GRADE SEROUS CARCINOMA, 0302 clinical medicine, Ovarian carcinoma, Aged, Carcinoma, DNA Methylation, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, MicroRNAs, Middle Aged, Mutation, Ovarian Neoplasms, RNA, Messenger, Genomics, Multidisciplinary, Genetics, HYBRID SELECTION, 0303 health sciences, female genital diseases and pregnancy complications, 3. Good health, Multidisciplinary Sciences, Serous fluid, BRCA MUTATION CARRIERS, 030220 oncology & carcinogenesis, DNA methylation, PARP inhibitor, Science & Technology - Other Topics, General Science & Technology, Biology, Article, 03 medical and health sciences, CLEAR-CELL CARCINOMA, MD Multidisciplinary, microRNA, HIGH-THROUGHPUT ANNOTATION, medicine, DRIVER MUTATIONS, Gene, 030304 developmental biology, Neoplastic, Science & Technology, MUTANT-CELLS, SOMATIC MUTATIONS, medicine.disease, CANCER STATISTICS, Gene Expression Regulation, Cancer research, RNA, Ovarian cancer
Abstract

A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients’ lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology., National Institutes of Health (U.S.) (Grant U54HG003067), National Institutes of Health (U.S.) (Grant U54HG003273), National Institutes of Health (U.S.) (Grant U54HG003079), National Institutes of Health (U.S.) (Grant U24CA126543), National Institutes of Health (U.S.) (Grant U24CA126544), National Institutes of Health (U.S.) (Grant U24CA126546), National Institutes of Health (U.S.) (Grant U24CA126551), National Institutes of Health (U.S.) (Grant U24CA126554), National Institutes of Health (U.S.) (Grant U24CA126561), National Institutes of Health (U.S.) (Grant U24CA126563), National Institutes of Health (U.S.) (Grant U24CA143882), National Institutes of Health (U.S.) (Grant U24CA143731), National Institutes of Health (U.S.) (Grant U24CA143835), National Institutes of Health (U.S.) (Grant U24CA143845), National Institutes of Health (U.S.) (Grant U24CA143858), National Institutes of Health (U.S.) (Grant U24CA144025), National Institutes of Health (U.S.) (Grant U24CA143866), National Institutes of Health (U.S.) (Grant U24CA143867), National Institutes of Health (U.S.) (Grant U24CA143848), National Institutes of Health (U.S.) (Grant U24CA143843), National Institutes of Health (U.S.) (Grant R21CA135877)

Published
2010

46. The experiences of Accession 8 migrants in England: Motivations, work and agency

Author

Cook, J, Dwyer, PJ, and Waite, L

Subjects
other, HM
Abstract

Drawing on a recently completed qualitative study in a northern English city, this paper explores motivations and experiences of Accession 8 (A8) migrants who have entered the United Kingdom following the expansion of the European Union in 2004. The paper considers commonalities and differences among the group of migrants routinely referred to as A8 migrant workers/labourers. Diversity is apparent in three particular respects: first, the motivations and forms of movement undertaken; second, their experiences of work within the UK paid labour market; and third, the extent to which the act and experience of migration offers new individual and collective opportunities and potentially opens up spaces for people to negotiate structural constraints and reconfigure aspects of their identity.

Published
2010

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