Disability-related inequalities in the prevalence of loneliness across the lifespan: trends from Australia, 2003 to 2020.

BACKGROUND: Experiencing loneliness can be distressing and increasing evidence indicates that being lonely is associated with poor physical and mental health outcomes. Cross-sectional studies have demonstrated that people with disability have increased risk of experiencing loneliness compared to people without disability. However, we do not know if these inequalities have changed over time. This study investigated the prevalence of loneliness for people with disability in Australia annually from 2003 to 2020 to examine whether disability-related inequalities in loneliness have changed over time, and disaggregated results for subgroups of people with disability by age group, sex, and disability group. METHODS: We used annual data (2003-2020) from the Household, Income and Labour Dynamics in Australia Survey. Loneliness was measured by a single question assessing the subjective experience of loneliness. For each wave, we calculated population-weighted age-standardised estimates of the proportion of people experiencing loneliness for people with and without disability. We then calculated the absolute and relative inequalities in loneliness between people with and without disability for each wave. Analyses were stratified by 10-year age groups, sex, and disability group (sensory or speech, physical, intellectual or learning, psychological, brain injury or stroke, other). RESULTS: From 2003 to 2020, the prevalence of loneliness was greater for people with disability, such that people with disability were 1.5 to 1.9 times more likely to experience loneliness than people without disability. While the prevalence of loneliness decreased for people without disability between 2003 and 2020, the prevalence of loneliness did not decrease for people with disability during this period. Inequalities in loneliness were more substantial for people with intellectual or learning disabilities, psychological disability, and brain injury or stroke. CONCLUSION: This study confirms that people with disability have increased risk of loneliness compared to people without disability. We add to the existing evidence by demonstrating that disability-related inequalities in loneliness have persisted for two decades in Australia without improvement. Our findings indicate that addressing inequalities in loneliness for people with disability is a critical public health concern given that loneliness is associated with a wide range of poor health outcomes.

Smoking Inequality Trends by Disability and Income in Australia, 2001 to 2020.

BACKGROUND: While policies to reduce smoking in many countries have been successful, disadvantaged groups (such as low-income groups) have only seen minor gains. People with disability are one such disadvantaged group and are more likely to smoke. However, evidence is limited on trends and inequalities in smoking for disabled people and on whether those also on low incomes are more likely to smoke. METHODS: We use annual data from 2001 to 2020 of the Household Income and Labour Dynamics in Australia survey. We use a Bayesian model to estimate smoking prevalence trends and inequalities for people with disability (2020, n = 1,370) and without disability (2020, n = 6,229) across the whole population and within income tertiles. To avoid reverse causation (smoking causing disability), we focus on younger people (15-44 years). RESULTS: Absolute reductions (per 100 people, [95% credible intervals]) in smoking were similar for people with (-13 [-16, -11]) and without disability (-15 [-16, -14]), with stable absolute but increasing relative inequalities. In the low-income group, absolute reductions in smoking prevalence for people with disability (-10 [-14, -6]) were smaller than in people without disability (-14 [-15, -12]), resulting in moderate evidence for increasing absolute inequalities (4 [0, 8]) and strong evidence for increasing relative inequalities. In high-income groups, disability-related absolute inequalities narrowed (-6 [-10, -3]), and relative inequalities were stable. CONCLUSIONS: Disabled people in Australia, especially those on low incomes, show signs of being left behind in efforts to reduce smoking.

Does employment status mediate the association between disability status and mental health among young adults? Evidence from the Household, Income and Labour Dynamics in Australia (HILDA) survey.

OBJECTIVE: Young adults with disabilities are less likely to be employed and more likely to have poor mental health than peers without disabilities. Growing evidence shows that social determinants of health may be causally related to mental health outcomes of people with disabilities. We aimed to assess if the disability to mental health association was mediated by employment status among young adults aged 20-35 years. METHODS: Four consecutive years (2016-2019) of data from the Household, Income and Labour Dynamics in Australia survey were used to conduct a causal mediation analysis. We decomposed the total causal effect of disability status on mental health (Short Form-36 Mental Health Inventory-5) into the natural direct effect from disability to mental health and the natural indirect effect representing the pathway through the employment mediator (being employed; being unemployed or wanting to work). RESULTS: 3435 participants (3058 with no disabilities, 377 with disabilities) were included in the analysis. The total causal effect of disability status on mental health was an estimated mean decrease in mental health of 4.84 points (95% CI -7.44 to -2.23). The indirect effect, through employment status, was estimated to be a 0.91-point decline in mental health (95% CI -1.50 to -0.31). CONCLUSIONS: Results suggest disability has an effect on the mental health of young adults; a proportion of this effect appears to operate through employment. The mental health of young adults with disabilities could potentially be improved with interventions to improve employment outcomes among this group, and by supporting individuals with disabilities into suitable employment.

A systematic review of the impact of the COVID-19 pandemic on the mental health of adolescents and young people with disabilities aged 15-29 years.

BACKGROUND: The COVID-19 pandemic has exacerbated the psychological burden on young people around the world and may have disproportionately large impacts for young people with disabilities. This review aims to systematically review the quantitative evidence on the impact of the COVID-19 pandemic on the mental health of young people with disabilities and evaluate the quality of included studies. METHODS: A systematic search was conducted using 5 electronic databases. The quality of the studies was assessed using the SIGN risk of bias assessment tool. A narrative synthesis was performed to synthesize the results of included studies. RESULTS: The initial search yielded 1935 studies, of which two met the eligibility criteria, one longitudinal study and one cross-sectional study, both assessed to be of low quality. In the cross-sectional study, young people with intellectual and developmental disabilities self-reported an increase in mental health symptoms. The longitudinal study found no evidence of a change in mental health symptoms from pre-pandemic to during the pandemic among young people with autism spectrum disorder, although these individuals reported negative impacts of the COVID-19 pandemic on their emotional or mental health. CONCLUSIONS: The findings of this review provide some weak evidence of a negative impact of the COVID-19 pandemic on the mental health of young people with disabilities. Importantly, the findings highlight the lack of research in this area. More research is needed to investigate the impact of the pandemic on the mental health of young disabled people, in order for governments to develop emergency preparedness plans to safeguard the well-being of this population.

Health and wellbeing outcomes associated with loneliness for people with disability: a scoping review.

BACKGROUND: Loneliness is a significant public health concern due to its detrimental impact on health and wellbeing. Despite people with disability reporting higher levels of loneliness than the general population, there has been little research into how this is affecting their health and wellbeing. In light of this, the aim of our study was to scope both the existing evidence about the health and wellbeing outcomes associated with loneliness for people with disability, as well as the conceptual frameworks and measures utilised in this field of research. METHODS: To conduct this scoping review, we followed the methodology outlined by JBI and searched MEDLINE, Scopus, Informit, Embase, and Web of Science for peer-reviewed, English-language articles published between 1 January 2000 and 8 February 2023. Two independent reviewers completed screening, full-text review and data extraction, with consensus sought at each stage. Data were analysed using content analysis and presented both numerically and narratively. RESULTS: Out of the initial 1602 publications identified in the scoping review, only nine were included after duplicate removal, title and abstract screening, and full-text review. This limited number of studies, with the earliest study one published in 2015, represents a key finding. Eight of the nine studies were quantitative, and all were conducted in high income countries. Most of these studies utilised a version of the University of Los Angles Loneliness Scale to measure loneliness and addressed specific impairment groups. Notably, most of the studies identified associations between loneliness and health and wellbeing outcomes for people with disability. CONCLUSIONS: This scoping review highlights the current scarcity of studies examining the effect that loneliness has on the health and wellbeing outcomes of people with disability. As most of the reviewed studies relied on loneliness measures designed for individuals without disability, they potentially overlook the unique life experiences of people with disability. Given that loneliness is an international public health concern, it is imperative that people with disability are not left behind or overlooked in efforts to address the impact of loneliness on health and wellbeing.

Disability and loneliness in the United Kingdom: cross-sectional and longitudinal analyses of trends and transitions.

BACKGROUND: Loneliness can have a detrimental impact on health, yet little is known about the association between disability and loneliness. METHODS: Secondary analysis of three waves of data collected between 2017 and 2020 by the UK's annual household panel study, Understanding Society. Direct age-standardisation was used to compare the prevalence of loneliness at each wave and the persistence of loneliness across all three waves for participants with/without disabilities aged 16-65 years. Transitional probabilities for the stability of loneliness, the stability of non-loneliness, the onset of loneliness and the offset of loneliness between consecutive waves were also estimated. RESULTS: At each wave, the prevalence of loneliness was significantly higher among respondents with disabilities than respondents without disabilities; these inequalities persisted with no evidence of change over time. The prevalence of persistent loneliness was 46% for respondents with disabilities compared with 22% for respondents without disabilities. Risk factors for the likelihood of persistent loneliness included disability, financial stress, not living as a couple, living in rented accommodation, being female and not being employed. The probability of the onset and stability of loneliness between successive waves were markedly higher for people with disabilities compared with people without disabilities. CONCLUSION: Adults with disabilities were more likely to experience loneliness, become lonely and remain lonely over time than their peers. Policies and interventions aimed at reducing loneliness should ensure that they are accessible and effective for people with disabilities. Further research is needed to explore the health outcomes of persistent loneliness among people with/without disabilities.

Trends in mental health inequalities for people with disability, Australia 2003 to 2020.

OBJECTIVE: Cross-sectional studies have demonstrated that people with disability have substantial inequalities in mental health compared to people without disability. However, it is not known if these inequalities have changed over time. This study compared the mental health of people with and without disability annually from 2003 to 2020 to investigate time trends in disability-related mental health inequalities. METHODS: We use annual data (2003-2020) of the Household, Income and Labour Dynamics in Australia Survey. Mental health was measured using the five-item Mental Health Inventory. For each wave, we calculated population-weighted age-standardised estimates of mean Mental Health Inventory scores for people with and without disability and calculated the mean difference in Mental Health Inventory score to determine inequalities. Analyses were stratified by age, sex and disability group (sensory or speech, physical, intellectual or learning, psychological, brain injury or stroke, other). RESULTS: From 2003 to 2020, people with disability had worse mental health than people without disability, with average Mental Health Inventory scores 9.8 to 12.1 points lower than for people without disability. For both people with and without disability, Mental Health Inventory scores decreased, indicating worsening mental health, reaching the lowest point for both groups in 2020. For some subpopulations, including young females and people with intellectual disability, brain injury or stroke, mental health inequalities worsened. CONCLUSION: This paper confirms that people with disability experience worse mental health than people without disability. We add to previous findings by demonstrating that disability-related inequalities in mental health have been sustained for a long period and are worsening in some subpopulations.

COVID-19 vaccination coverage and vaccine hesitancy among Australians with disability and long-term health conditions.

ISSUE ADDRESSED: COVID-19 vaccination is the cornerstone of managing Australia's COVID-19 pandemic and the success of the vaccination program depends on high vaccination coverage. This paper examined differences in COVID-19 vaccination coverage and vaccine hesitancy for people with disability, long-term health conditions, and carers - subgroups that were prioritised in Australia's vaccination program. METHODS: Using data from 2400 Australians who participated in two waves of the Taking the Pulse of the Nation survey in April and May 2021, we described vaccination coverage and hesitancy among people with disability, severe mental health conditions, severe long-term health conditions, frequent need for assistance with everyday activities, and carers. RESULTS: Vaccination coverage was estimated to be 8.2% in the population overall and was similar for people with disability, those with frequent need for assistance, and carers. It was higher for people with severe long-term health conditions (13.4%) and lower for people with severe mental health conditions (4.3%). Vaccine hesitancy was high overall (35.6%) and was similarly high across the priority groups, with only small differences for people with disability, severe long-term health conditions and frequent need for assistance. CONCLUSIONS: This study highlights a lack of difference in vaccination coverage for people with disability, long-term health conditions, and carers compared to the general population. So what? Sub-optimal vaccination coverage for people in the priority groups leaves many people at significant risk of serious disease or death if exposed to COVID-19, particularly in light of easing of disease-control restrictions across Australia and the emergence of new variants.

The impact of disability on employment and financial security following the outbreak of the 2020 COVID-19 pandemic in the UK.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic may have a greater impact on people with disabilities than non-disabled people. Our aim was to compare the short-term impact of the 2020 COVID-19 pandemic and first lockdown on the employment and financial security of working age adults with and without disabilities in the UK. METHODS: Secondary analysis of data collected in Wave 9 and the special April, May and June COVID-19 monthly surveys of 'Understanding Society', the UK's main annual household panel study. RESULTS: During the first 3 months of the introduction of the COVID-19 lockdown in the UK, respondents with disability were more likely than their peers to be working reduced hours and experience higher levels of financial stress. These differences were attenuated, but not eliminated, when estimates were adjusted to take account of pre-lockdown financial status. CONCLUSIONS: Working age adults with disability were particularly disadvantaged by the financial impact of the COVID-19 lockdown in the UK. The UN Secretary-General António Guterres has stated the need for a disability-inclusive COVID-19 government response. The results of our analysis suggest that these pleas have either not been heeded, or if measures have been implemented, they have so far been ineffectual in the UK.

Overt acts of perceived discrimination reported by British working-age adults with and without disability.

BACKGROUND: Exposure to discrimination can have a negative impact on health. There is little robust evidence on the prevalence of exposure of people with disabilities to discrimination, the sources and nature of discrimination they face, and the personal and contextual factors associated with increased risk of exposure. METHODS: Secondary analysis of de-identified cross-sectional data from the three waves of the UK's 'Life Opportunities Survey'. RESULTS: In the UK (i) adults with disabilities were over three times more likely than their peers to be exposed to discrimination, (ii) the two most common sources of discrimination were strangers in the street and health staff and (iii) discrimination was more likely to be reported by participants who were younger, more highly educated, who were unemployed or economically inactive, who reported financial stress or material hardship and who had impairments associated with hearing, memory/speaking, dexterity, behavioural/mental health, intellectual/learning difficulties and breathing. CONCLUSIONS: Discrimination faced by people with disabilities is an under-recognised public health problem that is likely to contribute to disability-based health inequities. Public health policy, research and practice needs to concentrate efforts on developing programs that reduce discrimination experienced by people with disabilities.

Hierarchical Models for International Comparisons: Smoking, Disability, and Social Inequality in 21 European Countries.

BACKGROUND: International comparisons of social inequalities in health outcomes and behaviors are challenging. Due to the level of disaggregation often required, data can be sparse and methods to make adequately powered comparisons are lacking. We aimed to illustrate the value of a hierarchical Bayesian approach that partially pools country-level estimates, reducing the influence of sampling variation and increasing the stability of estimates. We also illustrate a new way of simultaneously displaying the uncertainty of both relative and absolute inequality estimates. METHODS: We used the 2014 European Social Survey to estimate smoking prevalence, absolute, and relative inequalities for men and women with and without disabilities in 21 European countries. We simultaneously display smoking prevalence for people without disabilities (x-axis), absolute (y-axis), and relative inequalities (contour lines), capturing the uncertainty of these estimates by plotting a 2-D normal approximation of the posterior distribution from the full probability (Bayesian) analysis. RESULTS: Our study confirms that across Europe smoking prevalence is generally higher for people with disabilities than for those without. Our model shifts more extreme prevalence estimates that are based on fewer observations, toward the European mean. CONCLUSIONS: We demonstrate the utility of partial pooling to make adequately powered estimates of inequality, allowing estimates from countries with smaller sample sizes to benefit from the increased precision of the European average. Including uncertainty on our inequality plot provides a useful tool for evaluating both the geographical patterns of variation in, and strength of evidence for, differences in social inequalities in health.

Do financial hardship and social support mediate the effect of unaffordable housing on mental health?

PURPOSE: Unaffordable housing has a negative impact on mental health; however, little is known about the causal pathways through which it transmits this effect. We examine the role of financial hardship and social support as mediators of this relationship. METHODS: We identified households where housing costs changed from affordable to unaffordable across two waves of the Household, Income and Labour Dynamics in Australia (HILDA) Survey (2014-2015). The sequential causal mediation analysis was used to decompose the total effect of unaffordable housing on mental health into the portion attributable to financial hardship and social support [natural indirect effect (NIE)] and the portion not occurring through measured pathways [natural direct effect (NDE)]. Mental health was measured using the Mental Health Inventory (MHI) and Kessler psychological distress (KPD) scale. Baseline covariates included age, sex, household income, financial hardship, social support, marital status and employment status. Bootstrapping with 1000 replications was used to calculate 95% confidence intervals (CIs). Multiple imputations using chained equations were applied to account for missing data. RESULTS: Unaffordable housing led to a change in mean mental health score on the MHI scale (- 1.3, 95% CI: - 2.1, - 0.6) and KPDS scale (0.9, 95% CI: 0.4, 1.4). Financial hardship accounted for 54% of the total effect on MHI scale and 53% on KPD scale. Collectively, financial hardship and social support explained 68% of the total effect on MHI scale and 67% on KPD scale, respectively. CONCLUSIONS: In conclusion, the negative mental health effect of unaffordable housing is largely mediated through increased financial hardship.

The effect of gender on mental health service use: an examination of mediation through material, social and health-related pathways.

PURPOSE: We aimed to understand how much of the gender difference in mental health service use could be due to the joint mediation of employment, behavioural and material factors, social support and mental health need. METHODS: We used data from employed individuals aged 18-65 years who participated in the 2015-2017 waves of the Household, Income and Labour Dynamics in Australia survey. The exposure (male, female) and confounders were measured in 2015, mediators in 2016 and the outcome-whether a person had seen a mental health professional in the previous year-was measured in 2017. We estimated natural mediation effects using weighted counterfactual predictions from a logistic regression model. RESULTS: Men were less likely to see a mental health care provider than women. The total causal effect on the risk difference scale was - 0.045 (95% CI - 0.056, - 0,034). The counterfactual of men taking the mediator values of women explained 28% (95% CI 1.7%, 54%) of the total effect, with the natural direct effect estimated to represent an absolute risk difference of - 0.033 (95% CI - 0.048, - 0.018) and the natural indirect effect - 0.012 (95% CI - 0.022, - 0.0027). CONCLUSION: Gendered differences in the use of mental health services could be reduced by addressing inequalities in health, employment, material and behavioural factors, and social support.

The cumulative effect of living with disability on mental health in working-age adults: an analysis using marginal structural models.

PURPOSE: Previous studies have shown that acquiring a disability is associated with a reduction in mental health, but they have not considered the cumulative impact of having a disability on mental health. We used acquisition of a non-psychological disability to estimate the association of each additional year lived with disability on mental health (measured using the Mental Component Summary score of the Short Form Health Survey). METHODS: We used the first 13 waves of data (years 2001-2013) from the Household, Income and Labour Dynamics in Australia Survey. The sample included 4113 working-age (18-65 years) adults who were disability-free at waves 1 and 2. We fitted marginal structural models with inverse probability weights to estimate the association of each additional year of living with disability on mental health, employing multiple imputation to handle the missing data. RESULTS: Of the 4113 participants, 7.7 percent acquired a disability. On average, each additional year lived with disability was associated with a decrease in the mean Mental Component Summary score (ß = - 0.42; 95% CI - 0.71, - 0.14). CONCLUSIONS: This study provides evidence that each additional year lived with non-psychological disability is associated with a decline in mental health among working-age Australians.

Does the effect of disability acquisition on mental health differ by employment characteristics? A longitudinal fixed-effects analysis.

PURPOSE: Longitudinal studies have suggested a causal relationship between disability acquisition and mental health, but there is substantial heterogeneity in the magnitude of the effect. Previous studies have provided evidence that socioeconomic characteristics can buffer the effect but have not examined the role of employment characteristics. METHODS: We used data from 17 annual waves of the Household, Income and Labour Dynamics in Australia Survey to compare the mental health of working age individuals before and after disability acquisition, using the Mental Health Inventory, a subscale of the SF-36 health questionnaire. Linear fixed-effects regression models were used to estimate the effect of disability acquisition on mental health. We tested for effect modification by two characteristics of people's employment prior to disability acquisition: occupational skill level and contract type. Multiple imputation using chained equations was used to handle missing data. RESULTS: Disability acquisition was associated with a substantial decline in mental health score (estimated mean difference: - 4.3, 95% CI - 5.0, - 3.5). There was evidence of effect modification by occupational skill level, with the largest effects seen for those in low-skilled jobs (- 6.1, 95% CI - 7.6, - 4.5), but not for contract type. CONCLUSIONS: The findings highlight the need for social and health policies that focus on increasing employment rates, improving the sustainability of employment, and providing employment services and education and training opportunities for people who acquire a disability, particularly for people in low-skilled occupations, to reduce the mental health inequalities experienced by people with disabilities.

Predictors of Change in Employment Status and Associations with Quality of Life: A Prospective International Study of People with Multiple Sclerosis.

Purpose This prospective international study aimed to assess the changes in employment, and predictors thereof, and associated change in mental health quality of life in people with multiple sclerosis (MS). Methods People with MS were recruited online through social media, forums and newsletters to complete an online English-language survey in 2012 and again in 2015, to assess changes in employment and clinical characteristics. Results 1276 people with MS of working age were included of whom 35.9% were employed full time, 25.6% part-time, 3.1% were unemployed and seeking employment, 19.7% were retired due to disability and 15.7% were not in the labour force. Part/full time employment decreased from 61.4 to 57.1% of the sample 2.5 years later, and 25.5% experienced some change in employment status. Lower level of education and higher level of disability at baseline predicted loss of employment at follow-up. 62.0% of the sample indicated that MS impacted on employment over their lifetime, associated with a lower level of education and progressive MS at time of diagnosis. Retiring due to disability was predictive of a decreased mental health related QOL score. Conclusion Employment status was negatively impacted by MS for most participants. We showed for the first time that employment loss was prospectively associated with poorer mental health related quality of life. Employment support including vocational services, reasonable flexibility in the workplace, and legal protection against discrimination should be widely available to assist people with MS, especially for those with progressive onset MS, higher disability and lower levels of education who are at higher risk of employment loss.

Effectiveness of Exercise Interventions for Pain Reduction in People With Multiple Sclerosis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To systematically review the evidence of the effect of exercise compared with passive control on pain in people with multiple sclerosis. DATA SOURCE AND STUDY SELECTION: Five electronic databases were searched for randomized controlled trials published up to March 2017 that recruited people with multiple sclerosis where exercise was the intervention and pain was an outcome (PROSPERO registration number CRD42017060489). STATISTICAL ANALYSIS: A random-effects meta-analysis was conducted to estimate the standardized mean difference of the effect of exercise on pain between treatment and control groups. We assessed risk of bias, fitted meta-regression models to explore heterogeneity between studies, and assessed small study effects. DATA SYNTHESIS: Ten studies met the inclusion criteria (total sample size=389), and all studies were at high risk of bias. We found that exercise interventions were associated with less pain compared with passive control groups (standardized mean difference=-.46; 95% CI, -.92 to .00). There was high between-study heterogeneity (I2=77.0%), which was not explained by the prespecified study characteristics. There was also some evidence of small study effects. CONCLUSION: This is the first systematic review of the effect of exercise interventions on pain in people with multiple sclerosis, a chronic neurological disorder that affects 2.5 million people. We found some evidence that exercise compared with passive control alleviates pain in this population, but there were limitations in reporting and study quality with high risk of bias of individual studies and heterogeneity between studies.

Mental health of adolescents: variations by borderline intellectual functioning and disability.

Adolescence is a period of elevated stress for many young people, and it is possible that the challenges of adolescence are different for vulnerable groups. We aimed to document the depressive and anxiety symptoms, emotional-behavioural difficulties and suicidal/self-harming behaviours among adolescents with borderline intellectual functioning (BIF) or a disability, compared to those with neither disability nor BIF. Data were drawn from the nationally representative Longitudinal Study of Australian Children. Participants were 2950 adolescents with complete data for waves 3-6 (years 2008-2014), aged 14-15 years in 2014. Anxiety and depression symptoms and self-harming/suicidal thought/behaviours were self-reported. Emotional-behavioural difficulties items came from the Strengths and Difficulties Questionnaire, and were parent-, and adolescent-reported. Results of logistic regression analyses indicate that the emotional-behavioural difficulties of adolescents with either a disability or BIF, were worse than for those with neither disability nor BIF. While adolescents with a disability reported more anxiety symptoms, no clear associations were observed for self-harming/suicidal thoughts/behaviours or depressive symptoms for those with either BIF or a disability. Adolescents with BIF or a disability are at higher risk of poor mental health than those with neither disability nor BIF, and it is vital that factors contributing to these differences are identified in order to reduce these mental health inequalities.

Combining fixed effects and instrumental variable approaches for estimating the effect of psychosocial job quality on mental health: evidence from 13 waves of a nationally representative cohort study.

Background: Previous studies suggest that poor psychosocial job quality is a risk factor for mental health problems, but they use conventional regression analytic methods that cannot rule out reverse causation, unmeasured time-invariant confounding and reporting bias. Methods: This study combines two quasi-experimental approaches to improve causal inference by better accounting for these biases: (i) linear fixed effects regression analysis and (ii) linear instrumental variable analysis. We extract 13 annual waves of national cohort data including 13 260 working-age (18-64 years) employees. The exposure variable is self-reported level of psychosocial job quality. The instruments used are two common workplace entitlements. The outcome variable is the Mental Health Inventory (MHI-5). We adjust for measured time-varying confounders. Results: In the fixed effects regression analysis adjusted for time-varying confounders, a 1-point increase in psychosocial job quality is associated with a 1.28-point improvement in mental health on the MHI-5 scale (95% CI: 1.17, 1.40; P < 0.001). When the fixed effects was combined with the instrumental variable analysis, a 1-point increase psychosocial job quality is related to 1.62-point improvement on the MHI-5 scale (95% CI: -0.24, 3.48; P = 0.088). Conclusions: Our quasi-experimental results provide evidence to confirm job stressors as risk factors for mental ill health using methods that improve causal inference.

Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2.

We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios [OR] = 0.90 [0.88-0.92]; P-value = 1.58 × 10(-25)). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans ∼14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 [1.08-1.17]; P-value = 7.89 × 10(-09)) and rs13294895 (OR = 1.09 [1.06-1.12]; P-value = 2.97 × 10(-11)). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 [1.06-1.18]; P-value = 2.77 × 10(-05)). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-α, FOXA1 and GATA-3. In vitro analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the KLF4 gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis.