Novel genes and sex differences in COVID-19 severity

Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.Instituto de Salud Carlos III (COV20_00622 to A.C., COV20/00792 to M.B., COV20_00181 to C.A., COV20_1144 to M.A.J.S., PI20/00876 to C.F.); European Union (ERDF) ‘A way of making Europe’. Fundación Amancio Ortega, Banco de Santander (to A.C.), Estrella de Levante S.A. and Colabora Mujer Association (to E.G.-N.) and Obra Social La Caixa (to R.B.); Agencia Estatal de Investigación (RTC-2017-6471-1 to C.F.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.)

Use of personal child health records in the UK: findings from the millennium cohort study.

OBJECTIVES: The personal child health record (PCHR) is a record of a child's growth, development, and uptake of preventive health services, designed to enhance communication between parents and health professionals. We examined its use throughout the United Kingdom with respect to recording children's weight and measures of social disadvantage and infant health. DESIGN: Cross sectional survey within a cohort study. SETTING: UK. PARTICIPANTS: Mothers of 18,503 children born between 2000 and 2002, living in the UK at 9 months of age. MAIN OUTCOME MEASURES: Proportion of mothers able to produce their child's PCHR; proportion of PCHRs consulted containing record of child's last weight; effective use of the PCHR (defined as production, consultation, and child's last weight recorded). RESULTS: In all, 16,917 (93%) mothers produced their child's PCHR and 15,138 (85%) mothers showed effective use of their child's PCHR. Last weight was recorded in 97% of PCHRs consulted. Effective use was less in children previously admitted to hospital, and, in association with factors reflecting social disadvantage, including residence in disadvantaged communities, young maternal age, large family size (four or more children; incidence rate ratio 0.87; 95% confidence interval 0.83 to 0.91), and lone parent status (0.88; 0.86 to 0.91). CONCLUSIONS: Use of the PCHR is lower by women living in disadvantaged circumstances, but overall the record is retained and used by a high proportion of all mothers throughout the UK in their child's first year of life. PCHR use is endorsed in the National Service Framework for Children and has potential benefits which extend beyond the direct care of individual children

An ecological systems approach to examining risk factors for early childhood overweight: findings from the UK Millennium Cohort Study

Objective: To use an ecological systems approach to examine individual-, family-, community- and area-level risk factors for overweight (including obesity) in 3-year-old children. Methods: A prospective nationally representative cohort study conducted in England, Wales, Scotland, Northern Ireland. Participants included 13 188 singleton children aged 3 years in the Millennium Cohort Study, born between 2000 and 2002, who had complete height/weight data. The main outcome measure was childhood overweight (including obesity) defined by the International Obesity TaskForce cut-offs for body mass index. Results: 23.0% of 3-year-old children were overweight or obese. In the fully adjusted model, primarily individual- and family-level factors were associated with early childhood overweight: birthweight z-score (adjusted odds ratio, 1.36, 95% CI 1.30 to 1.42), black ethnicity (1.41, 1.11 to 1.80) (compared with white), introduction to solid foods or =21 hours/week (1.23, 1.10 to 1.37) (compared with never worked). Breastfeeding > or =4 months (0.86, 0.76 to 0.97) (compared with none) and Indian ethnicity (0.63, 0.42 to 0.94) were associated with a decreased risk of early childhood overweight. Children from Wales were also more likely to be overweight than children from England. Conclusions: Most risk factors for early childhood overweight are modifiable or would allow at-risk groups to be identified. Policies and interventions should focus on parents and providing them with an environment to support healthy behaviours for themselves and their children

Maternal employment and early childhood overweight: findings from the UK Millennium Cohort Study

Background: In most developed countries, maternal employment has increased rapidly. Changing patterns of family life have been suggested to be contributing to the rising prevalence of childhood obesity. Objectives: Our primary objective was to examine the relationship between maternal and partner employment and overweight in children aged 3 years. Our secondary objective was to investigate factors related to early childhood overweight only among mothers in employment. Design: Cohort study. Subjects: A total of 13 113 singleton children aged 3 years in the Millennium Cohort Study, born between 2000 and 2002 in the United Kingdom, who had complete height/weight data and parental employment histories. Measurements: Parents were interviewed when the child was aged 9 months and 3 years, and the child's height and weight were measured at 3 years. Overweight (including obesity) was defined by the International Obesity Task Force cut-offs. Results: A total of 23% (3085) of children were overweight at 3 years. Any maternal employment after the child's birth was associated with early childhood overweight (odds ratio (OR) [95% confidence interval (CI)]; 1.14 [1.00, 1.29]), after adjustment for potential confounding and mediating factors. Children were more likely to be overweight for every 10 h a mother worked per week (OR [95% CI]; 1.10 [1.04, 1.17]), after adjustment. An interaction with household income revealed that this relationship was only significant for children from households with an annual income of pound33 000 ($57 750) or higher. There was no evidence for an association between early childhood overweight and whether or for how many hours the partner worked, or with mothers' or partners' duration of employment. These relationships were also evident among mothers in employment. Independent risk factors for early childhood overweight were consistent with the published literature. Conclusions: Long hours of maternal employment, rather than lack of money may impede young children's access to healthy foods and physical activity. Policies supporting work-life balance may help parents reduce potential barriers

Feasibility of collecting oral fluid samples in the home setting to determine seroprevalence of infections in a large-scale cohort of preschool-aged children

Oral fluid is a non-invasive biological sample, which can be returned by post, making it suitable for large-scale epidemiological studies in children. We report our experience of oral fluid collection from 14 373 preschool-aged children in the UK Millennium Cohort Study. Samples were collected by mothers in the home setting following the guidance of trained interviewers, and posted to the laboratory. Samples were received from 11698 children (81.4 %). Children whose mothers were of Black Caribbean ethnicity and who lived in non-English-speaking households were less likely to provide a sample, and those with a maternal history of asthma more likely to provide a sample [adjusted risk ratio (95 % CI) 0.85 (0.73-0.98), 0.87 (0.77-0.98) and 1.03 (1.00-1.05) respectively]. Collection of oral fluid samples is feasible and acceptable in large-scale child cohort studies. Formal interpreter support may be required to increase participation rates in surveys that collect biological samples from ethnic minorities

Regional differences in overweight: an effect of people or place?

Objective: To examine UK country and English regional differences in childhood overweight (including obesity) at 3 years and determine whether any differences persist after adjustment for individual risk factors. Design: Nationally representative prospective study. Setting: England, Wales, Scotland and Northern Ireland. Participants: 13 194 singleton children from the UK Millennium Cohort Study with height and weight data at age 3 years. Main outcome measure: Overweight (including obesity) was defined according to the International Obesity TaskForce cut-offs for body mass index, which are age and sex specific. Results: At 3 years of age, 23% (3102) of children were overweight or obese. In univariable analyses, children from Northern Ireland (odds ratio 1.30, 95% confidence interval 1.14 to 1.48) and Wales (1.26, 1.11 to 1.44) were more likely to be overweight than children from England. There were no differences in overweight between children from Scotland and England. Within England, children from the East (0.71, 0.57 to 0.88) and South East regions (0.82, 0.68 to 0.99) were less likely to be overweight than children from London. There were no differences in overweight between children from other English regions and children from London. These differences were maintained after adjustment for individual socio-demographic characteristics and other risk factors for overweight. Conclusions: UK country and English regional differences in early childhood overweight are independent of individual risk factors. This suggests a role for policies to support environmental changes that remove barriers to physical activity or healthy eating in young children

Novel genes and sex differences in COVID-19 severity

Here, we describe the results of a genome-wide study conducted in 11939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P= 60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.Peer reviewe

The association between overall health, psychological distress, and occupational heat stress among a large national cohort of 40,913 Thai workers

BACKGROUND Occupational heat stress is a well-known problem, particularly in tropical countries, affecting workers, health and well-being. There are very few recent studies that have reported on the effect of heat stress on mental health, or overall health in workers, although socioeconomic development and rapid urbanization in tropical developing countries like Thailand create working conditions in which heat stress is likely. OBJECTIVE This study is aimed at identifying the relationship between self-reported heat stress and psychological distress, and overall health status in Thai workers. RESULTS 18% of our large national cohort (>40,000 subjects) often works under heat stress conditions and males are exposed to heat stress more often than females. Furthermore, working under heat stress conditions is associated with both worse overall health and psychological distress (adjusted odds ratios ranging from 1.49 to 1.84). CONCLUSIONS This association between occupational heat stress and worse health needs more public health attention and further development on occupational health interventions as climate change increases Thailand's temperatures.This study was supported by the International Collaborative Research Grants Scheme with joint grants from the Wellcome Trust UK (GR0587MA) and the Australian NHMRC (268055)

Novel genes and sex differences in COVID-19 severity

Here, we describe the results of a genome-wide study conducted in 11939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P= 60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.Instituto de Salud Carlos III European Commission COV20_00622 COV20/00792 COV20_00181 COV20_1144 PI20/00876European Union (ERDF) 'A way of making Europe'Fundacion Amancio Ortega, Banco de SantanderEstrella de Levante S.A.Colabora Mujer AssociationLa Caixa FoundationAgencia Estatal de Investigacion RTC-2017-6471-1Cabildo Insular de Tenerife (Apuestas cientificas del ITER para colaborar en la lucha contra la COVID-19) CGIEU0000219140Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias PIFIISC20/5