Gout is a common arthritis caused by elevated serum uric acid (SUA) levels. Here we investigated loci influencing SUA in a genome-wide meta-analysis with 121,745 Japanese subjects. We identified 8948 variants at 36 genomic loci ( P <5 × 10 –8 ) including eight novel loci. Of these, missense variants of SESN2 and PNPLA3 were predicted to be damaging to the function of these proteins; another five loci— TMEM18 , TM4SF4 , MXD3-LMAN2 , PSORS1C1-PSORS1C2 , and HNF4A —are related to cell metabolism, proliferation, or oxidative stress; and the remaining locus, LINC01578 , is unknown. We also identified 132 correlated genes whose expression levels are associated with SUA-increasing alleles. These genes are enriched for the UniProt transport term, suggesting the importance of transport-related genes in SUA regulation. Furthermore, trans-ethnic meta-analysis across our own meta-analysis and the Global Urate Genetics Consortium has revealed 15 more novel loci associated with SUA. Our findings provide insight into the pathogenesis, treatment, and prevention of hyperuricemia/gout.

We identified a novel genetic variant associated with regular leisure-time exercise behavior. Further functional studies are required to validate the role of these variants in exercise behavior.

Both perceived stress and coping strategies may be associated with systemic inflammation in Japanese men, yet caution must be exercised before accepting the stress-inflammation-disease pathway.

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ObjectivesGenome-wide meta-analyses of clinically defined gout were performed to identify subtype-specific susceptibility loci. Evaluation using selection pressure analysis with these loci was also conducted to investigate genetic risks characteristic of the Japanese population over the last 2000–3000 years.MethodsTwo genome-wide association studies (GWASs) of 3053 clinically defined gout cases and 4554 controls from Japanese males were performed using the Japonica Array and Illumina Array platforms. About 7.2 million single-nucleotide polymorphisms were meta-analysed after imputation. Patients were then divided into four clinical subtypes (the renal underexcretion type, renal overload type, combined type and normal type), and meta-analyses were conducted in the same manner. Selection pressure analyses using singleton density score were also performed on each subtype.ResultsIn addition to the eight loci we reported previously, two novel loci, PIBF1 and ACSM2B, were identified at a genome-wide significance level (p<5.0×10–8) from a GWAS meta-analysis of all gout patients, and other two novel intergenic loci, CD2-PTGFRN and SLC28A3-NTRK2, from normal type gout patients. Subtype-dependent patterns of Manhattan plots were observed with subtype GWASs of gout patients, indicating that these subtype-specific loci suggest differences in pathophysiology along patients’ gout subtypes. Selection pressure analysis revealed significant enrichment of selection pressure on ABCG2 in addition to ALDH2 loci for all subtypes except for normal type gout.ConclusionsOur findings on subtype GWAS meta-analyses and selection pressure analysis of gout will assist elucidation of the subtype-dependent molecular targets and evolutionary involvement among genotype, phenotype and subtype-specific tailor-made medicine/prevention of gout and hyperuricaemia.

BackgroundNon-participation in second surveys is reported to be associated with certain baseline characteristics; however, such data are unavailable for Japanese populations. Although disease incidence during follow-up might influence participation, few reports have addressed this possibility. This study sought to identify factors associated with non-participation in a second survey of a population-based cohort, and to evaluate the influence of self-reported disease incidence on non-participation.MethodsAfter excluding participants who left the area (n = 423), died (n = 163), and withdrew from the study (n = 9) among 12 078 participants in a baseline survey for the Japan Multi-Institutional Collaborative Cohort Study in the Saga region between 2005 and 2007, 11 483 people were invited by mail to participate in a face-to-face second survey between 2010 and 2012. The 5-year clinical health history of non-participants was assessed by mail or telephone. Baseline characteristics and self-reported clinical outcomes of non-participants were compared with those of participants.ResultsAmong 11 483 people, 8454 (73.6%) participated in the second survey, and 2608 out of 3029 non-participants answered mail or telephone health surveys. Female sex, youngest and oldest ages, lower education, lower occupational class, current smoking, lower physical activity level, shorter sleep time, obesity, and constipation were associated with non-participation. Light drinking (0.1–22.9 g ethanol/day) was associated with participation. Non-participants reported a significantly higher incidence of cancer and a significantly lower proportion of hypertension compared with participants.ConclusionsBoth baseline characteristics and disease incidence during the follow-up period had significant associations with non-participation in the face-to-face second survey.

BackgroundAccumulated evidence suggests a weak positive relationship between psychosocial stress and body mass index (BMI), but little is known about stress coping strategies and BMI.ObjectiveWe aimed to examine if perceived stress and coping strategies are related to BMI, with any of their mutual interactions on BMI.MethodsThis cross-sectional study included 5,063 men and 6,982 women aged 40-69 years. A self-administered questionnaire ascertained perceived stress and 5 items of coping strategies (emotion expression, emotional support seeking, positive reappraisal, problem solving, and disengagement). Analyses were performed by gender with adjustment for age, socioeconomic status, and lifestyle factors.ResultsNo significant associations were detected between perceived stress and BMI in either men (P trend = 0.09) or women (P trend = 0.58). In men, however, ‘disengagement’ showed an inverse association with BMI (P trend < 0.001), and ‘positive reappraisal’ and ‘problem solving’ revealed a positive association with BMI (P trend = 0.04 and 0.007, respectively) even after controlling for perceived stress. A possible interaction between perceived stress and ‘disengagement’ on BMI was found in men (P interaction = 0.027); the inverse association between ‘disengagement’ and BMI was more evident in higher levels of stress (β = −0.13, P trend = 0.21 in low; β = −0.22, P trend = 0.01 in medium; and β = −0.24, P trend = 0.06 in high). In men, ‘disengagement’ was inversely associated with overweight/obesity (odds ratio 0.79, 95% confidential interval 0.67-0.95), and “positive reappraisal” was positively associated with it (1.25, 1.02-1.54).ConclusionsCoping strategies may have an important role in developing overweight/obesity, particularly in men.

Few studies have investigated deployment-related experiences of healthcare workers dispatched for medical humanitarian aid or attempted to assess their difficult living and working environments. This is the first study to develop and validate a scale to measure these kinds of difficulties, in 264 Japanese healthcare workers. The Humanitarian Aid Difficulty Scale was developed in three stages. First, an item pool was generated based on literature and expert reviews. The scale was then tested in a pilot study. Reliability and validity were identified through exploratory and confirmatory factor analysis and Cronbach's alpha. The scale consisted of 23 items across five factors based on exploratory factor analysis (cooperation, health status, infrastructure, culture and customs, and supplies and equipment). The total variance explained was 60.7%. Reliability of the five factors was acceptable and validity was supported by confirmatory factor analysis. Cronbach's alpha for the scale was 0.87. The scale may enable evaluation of the level of difficulty of the living and working environments of Japanese healthcare workers in medical humanitarian aid who are at a greater risk of distress.