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Abstract Background Paget's disease of bone (PDB) disrupts normal bone architecture and causes pain, deformity, deafness, osteoarthritis, and fractures. Genetic factors play a role in PDB and genetic tests are now conducted for research purposes. It is thus timely to investigate the potential for a clinical programme of genetic testing and preventative treatment for people who have a family history of PDB. This study examines the beliefs of relatives of people with PDB. It focuses particularly on illness and treatment representations as predictors of the acceptability and uptake of potential clinical programmes. Illness representations are examined using Leventhal's Common Sense Self-Regulation Model while cognitions about treatment behaviours (acceptance of testing and treatment uptake) are conceptualised within the Theory of Planned Behaviour. Methods/Design A postal questionnaire of non-affected relatives of people with Paget's disease. The sample will include relatives of Paget's patients with a family history of Paget's disease and relatives of Paget's patients without a family history of Paget's disease. The questionnaire will explore whether a range of factors relate to acceptability of a programme of genetic testing and preventive treatment in relatives of Paget's disease sufferers. The questionnaire will include several measures: illness representations (as measured by the Brief Illness Perceptions Questionnaire); treatment representations (as measured by Theory of Planned Behaviour-based question items, informed by a prior interview elicitation study); descriptive and demographic details; and questions exploring family environment and beliefs of other important people. Data will also be collected from family members who have been diagnosed with Paget's disease to describe the disease presentation and its distribution within a family. Discussion The answers to these measures will inform the feasibility of a programme of genetic testing and preventive treatment for individuals who are at a high risk of developing Paget's disease because they carry an appropriate genetic mutation. They will also contribute to theoretical and empirical approaches to predicting diagnostic and treatment behaviours from the combined theoretical models.

Background: Paget's disease of bone (PDB) disrupts normal bone architecture and causes pain, deformity, deafness, osteoarthritis, and fractures. Genetic factors play a role in PDB and genetic tests are now conducted for research purposes. It is thus timely to investigate the potential for a clinical programme of genetic testing and preventative treatment for people who have a family history of PDB. This study examines the beliefs of relatives of people with PDB. It focuses particularly on illness and treatment representations as predictors of the acceptability and uptake of potential clinical programmes. Illness representations are examined using Leventhal's Common Sense Self-Regulation Model while cognitions about treatment behaviours (acceptance of testing and treatment uptake) are conceptualised within the Theory of Planned Behaviour.Methods/design: A postal questionnaire of non-affected relatives of people with Paget's disease. The sample will include relatives of Paget's patients with a family history of Paget's disease and relatives of Paget's patients without a family history of Paget's disease. The questionnaire will explore whether a range of factors relate to acceptability of a programme of genetic testing and preventive treatment in relatives of Paget's disease sufferers. The questionnaire will include several measures: illness representations (as measured by the Brief Illness Perceptions Questionnaire); treatment representations (as measured by Theory of Planned Behaviour-based question items, informed by a prior interview elicitation study); descriptive and demographic details; and questions exploring family environment and beliefs of other important people. Data will also be collected from family members who have been diagnosed with Paget's disease to describe the disease presentation and its distribution within a family.Discussion: The answers to these measures will inform the feasibility of a programme of genetic testing and preventive treatment for individuals who are at a high risk of developing Paget's disease because they carry an appropriate genetic mutation. They will also contribute to theoretical and empirical approaches to predicting diagnostic and treatment behaviours from the combined theoretical models. [ABSTRACT FROM AUTHOR]

Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia.

Published guidelines adopted in many countries recommend that women whose family history of breast cancer places them at a risk>or=1.7 times that of the age-matched general population, should be considered for inclusion in special surveillance programmes. However validation of risk assessment models has been called for as a matter of urgency. The databases of the four Scottish Familial Breast Cancer clinics and the Scottish Cancer Registry have been searched to identify breast cancers occurring among 1,125 women aged 40-56, with family histories placing them below the "moderate" level of genetic risk. The observed incidence over 6 years was compared with age-specific data for the Scottish population. Our findings confirm that when there are two affected relatives (one first degree) the relative risk (RR) exceeds 1.7 regardless of their ages at diagnosis. When only one (first degree) relative was affected at any age from 40 to 55, the RR does not reach 1.7 if that relative was a mother but exceeds it if the relative was a sister. The probable explanation is that sisters are more likely than mother/daughter pairs to share homozygosity for a risk allele. Surveillance programmes might therefore accommodate sisters of women affected before age 55. Evidence that "low penetrance" alleles contributing to breast cancer risk may be recessive should be taken into account in strategies for identifying them.