Genetic polymorphism of pleiotrophin is associated with pain experience in Japanese adults Case-control study

Genetic factors play a role in individual differences in pain experience. Here, we performed a genome-wide association study (GWAS) to identify novel loci regulating pain processing. We conducted a 2-stage GWAS and the candidate single-nucleotide polymorphisms (SNPs) association study on pain experience using an exploratory cohort of patients with cancer pain. The confirmatory cohort comprised of participants from the general population with and without habitual use of analgesic medication. In the exploratory cohort, we evaluated pain intensity using a numerical rating scale, recorded daily opioid dosages, and calculated pain reduction rate. In the confirmatory cohort, pain experience was defined as habitual nonsteroidal anti-inflammatory drug usage. Using linear regression models, we identified candidate SNP in the exploratory samples, and tested the association between phenotype and experienced pain in the confirmatory samples. We found 1 novel SNP (rs11764598)—located on the gene encoding for pleiotrophin on chromosome 7—that passed the genome-wide suggestive significance at 20% false discovery rate (FDR) correction in the exploratory samples of patients with cancer pain (P = 1.31 × 10-7, FDR = 0.101). We confirmed its significant association with daily analgesic usage in the confirmatory cohort (P = .028), although the minor allele affected pain experience in an opposite manner. We identified a novel genetic variant associated with pain experience. Further studies are required to validate the role of pleiotrophin in pain processing

Association of exposure level to passive smoking with hypertension among lifetime nonsmokers in Japan : a cross-sectional study

Brief exposure to passive smoking immediately elevates blood pressure. However, little is known about the association between exposure to passive smoking and chronic hypertension. We aimed to examine this association in a cross-sectional study, after controlling multiple potential confounders. Participants included 32,098 lifetime nonsmokers (7,216 men and 24,882 women) enrolled in the Japan Multi-Institutional Collaborative Cohort Study. Passive smoking was assessed using a self-administered questionnaire. The single question about exposure to passive smoking had five response options: “sometimes or almost never,” “almost every day, 2 hours/day or less,” “almost every day, 2 to 4 hours/day,” “almost every day, 4 to 6 hours/day,” and “almost every day, 6 hours/day or longer.” Hypertension was defined as any of the following: systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or use of antihypertensive medication. Multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) for hypertension were estimated by exposure level to passive smoking using unconditional logistic regression models. The multivariate-adjusted OR for hypertension in those exposed almost every day was 1.11 (95% CI: 1.03–1.20) compared with those exposed sometimes or almost never. The OR for a 1-hour per day increase in exposure was 1.03 (95% CI: 1.01–1.06, P for trend = .006). This association was stronger in men than in women; the ORs were 1.08 (95% CI: 1.01–1.15, P for trend = .036) and 1.03 (95% CI: 1.00–1.05, P for trend = .055), respectively. Our findings suggest importance of tobacco smoke control for preventing hypertension

Polymorphisms and Body Mass Index Across Life Course

Background: Obesity is a reported risk factor for various health problems. Genome-wide association studies (GWASs) have identified numerous independent loci associated with body mass index (BMI). However, most of these have been focused on Europeans, and little evidence is available on the genetic effects across the life course of other ethnicities. Methods: We conducted a cross-sectional study to examine the associations of 282 GWAS-identified single nucleotide polymorphisms with three BMI-related traits, current BMI, BMI at 20 years old (BMI at 20), and change in BMI (BMI change), among 11,586 Japanese individuals enrolled in the Japan Multi-Institutional Collaborative Cohort study. Associations were examined using multivariable linear regression models. Results: We found a significant association (P < 0.05/282 = 1.77 × 10−4) between BMI and 11 polymorphisms in or near FTO, BDNF, TMEM18, HS6ST3, and BORCS7. The trend was similar between current BMI and BMI change, but differed from that of the BMI at 20. Among the significant variants, those on FTO were associated with all BMI traits, whereas those on TMEM18 and HS6SR3 were only associated with BMI at 20. The association of FTO loci with BMI remained, even after additional adjustment for dietary energy intake. Conclusions: Previously reported BMI-associated loci discovered in Europeans were also identified in the Japanese population. Additionally, our results suggest that the effects of each loci on BMI may vary across the life course and that this variation may be caused by the differential effects of individual genes on BMI via different pathways

A genome-wide association study on meat consumption in a Japanese population : the Japan Multi-Institutional Collaborative Cohort study

Recent genome-wide association studies (GWAS) on the dietary habits of the Japanese population have shown that an effect rs671 allele was inversely associated with fish consumption, whereas it was directly associated with coffee consumption. Although meat is a major source of protein and fat in the diet, whether genetic factors that influence meat-eating habits in healthy populations are unknown. This study aimed to conduct a GWAS to find genetic variations that affect meat consumption in a Japanese population. We analysed GWAS data using 14 076 participants from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study. We used a semi-quantitative food frequency questionnaire to estimate food intake that was validated previously. Association of the imputed variants with total meat consumption per 1000 kcal energy was performed by linear regression analysis with adjustments for age, sex, and principal component analysis components 1–10. We found that no genetic variant, including rs671, was associated with meat consumption. The previously reported single nucleotide polymorphisms that were associated with meat consumption in samples of European ancestry could not be replicated in our J-MICC data. In conclusion, significant genetic factors that affect meat consumption were not observed in a Japanese population

Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals

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

A Genome-wide Association Study on Confection Consumption in a Japanese Population- The Japan Multi-Institutional Collaborative Cohort study.

Differences in individual eating habits may be influenced by genetic factors, in addition to cultural, social, or environmental factors. Previous studies suggested that genetic variants within sweet taste receptor genes family were associated with sweet taste perception and the intake of sweet foods. The aim of this study was to conduct a genome-wide association study (GWAS) to find genetic variations that affect confection consumption in a Japanese population. We analyzed GWAS data on sweets consumption using 14,073 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a semi-quantitative food frequency questionnaire to estimate food intake that was validated previously. Association of the imputed variants with sweets consumption was performed by linear regression analysis with adjustments for age, sex, total energy intake and principal component analysis components 1 to 3. Furthermore, the analysis was repeated adjusting for alcohol intake (g/day) in addition to the above-described variables. We found 418 single nucleotide polymorphisms (SNPs) located in 12q24 that were associated with sweets consumption. SNPs with the 10 lowest P-values were located on nine genes including at the BRAP, ACAD10, and ALDH2 regions on 12q24.12-13. After adjustment for alcohol intake, no variant was associated with sweets intake with genome-wide significance. In conclusion, we found a significant number of SNPs located on 12q24 genes that were associated with sweets intake before adjustment for alcohol intake. However, all of them lost statistical significance after adjustment for alcohol intake

Detection of UVBR-sensitive and -tolerant bacteria in surface waters of the western North Pacific

In order to evaluate the effects of solar ultraviolet radiation (UVR) on eubacterial community composition, we examined the tolerance of eubacterial phylotypes to solar UV radiation in surface waters of the western North Pacific during September 2005. Bromodeoxyuridine (BrdU), a halogenated thymine analogue, was used for labeling newly synthesized DNA in proliferating cells. Thymine dimers (TD), which are specifically formed in DNA by biologically harmful ultraviolet B radiation (UVBR; 280-315 nm), were also applied to detect UVB damaged genomes selectively. PCR-denaturing gradient gel electrophoresis (PCR-DGGE) on the labeled samples revealed that UVBR-resistant cells showing active synthesis of DNA without accumulating TD, varied among phylotypes. In addition, UVBR-sensitive band positions with TD indicated inter-specific variations in sensitivity to UVBR. Phylogenetic analysis revealed that 12 DNA sequences were classified into 8 phylogenetic groups: 3 Rosecbacter, 1 Sphingomonas, 2 Gammaproteobacteria, 1 Actinobacteria, 1 Synechococcus, 2 Prochlorococcus, 1 plastid and 1 another group. A UVBR-resistant phylotype was affiliated to Erythrobacter sp. (previously designated as Sphingomonas sp.), which was distributed in warmer waters from the south of Oyashio to Kuroshio regions. A UVBR-sensitive phylotype was affiliated to Pseudoalteromonas sp. in Gammaproteobacteria. Dominant heterotrophic eubacteria were composed of both sensitive and resistant phylotypes. This is the first report on TD accumulated eubacterial phylotypes in oceanic surface waters