Obesity is a risk factor for a wide variety of health problems. In a genome-wide association study (GWAS) of body mass index (BMI) in Japanese people (n = 173,430), we found 85 loci significantly ...associated with obesity (P < 5.0 × 10
), of which 51 were previously unknown. We conducted trans-ancestral meta-analyses by integrating these results with the results from a GWAS of Europeans and identified 61 additional new loci. In total, this study identifies 112 novel loci, doubling the number of previously known BMI-associated loci. By annotating associated variants with cell-type-specific regulatory marks, we found enrichment of variants in CD19
cells. We also found significant genetic correlations between BMI and lymphocyte count (P = 6.46 × 10
, r
= 0.18) and between BMI and multiple complex diseases. These findings provide genetic evidence that lymphocytes are relevant to body weight regulation and offer insights into the pathogenesis of obesity.
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IJS, NUK, SBMB, UL, UM, UPUK
The sweet taste preference of humans is an important adaptation to ensure the acquisition of carbohydrate nutrition; however, overconsumption of sweet foods can potentially lead to diseases such as ...obesity and diabetes. Although previous studies have suggested that interindividual variation of human sweet taste preference is heritable, genetic loci associated with the trait have yet to be fully elucidated. Here, we genotyped 12,312 Japanese participants using the HumanCore-12+ Custom BeadChip or the HumanCore-24 Custom BeadChip microarrays. The sweet taste preference of the participants was surveyed via an internet-based questionnaire, resulting in a five-point scale of sweet taste preference. The genome-wide meta-analysis of the Japanese participants revealed a strong association between the 12q24 locus and sweet taste preference scale (P = 2.8 × 10−70). The lead variant rs671 is monoallelic in non-East Asian populations and is located in the aldehyde dehydrogenase (ALDH2) gene, encoding an enzyme involved in alcohol metabolism. The association between the minor allele of rs671 and sweet taste preference was attenuated by adjusting for alcohol drinking. The subgroup analysis showed that the effect of rs671 on sweet taste preference was greater in males than in females. In conclusion, we found an association between the 12q24 locus and sweet taste preference in the Japanese population, and showed that the adjustment for drinking habits attenuated the association. This novel genetic association may provide new clues to elucidate mechanisms determining sweet taste preferences.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We established a community-based cohort study to assess the long-term impact of the Great East Japan Earthquake on disaster victims and gene-environment interactions on the incidence of major ...diseases, such as cancer and cardiovascular diseases.
We asked participants to join our cohort in the health check-up settings and assessment center based settings. Inclusion criteria were aged 20 years or over and living in Miyagi or Iwate Prefecture. We obtained information on lifestyle, effect of disaster, blood, and urine information (Type 1 survey), and some detailed measurements (Type 2 survey), such as carotid echography and calcaneal ultrasound bone mineral density. All participants agreed to measure genome information and to distribute their information widely.
As a result, 87,865 gave their informed consent to join our study. Participation rate at health check-up site was about 70%. The participants in the Type 1 survey were more likely to have psychological distress than those in the Type 2 survey, and women were more likely to have psychological distress than men. Additionally, coastal residents were more likely to have higher degrees of psychological distress than inland residents, regardless of sex.
This cohort comprised a large sample size and it contains information on the natural disaster, genome information, and metabolome information. This cohort also had several detailed measurements. Using this cohort enabled us to clarify the long-term effect of the disaster and also to establish personalized prevention based on genome, metabolome, and other omics information.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Several studies suggest the involvement of dietary habits and gut microbiome in allergic diseases. However, little is known about the nutritional and gut microbial factors associated with the risk of ...allergic rhinitis (AR). We recruited 186 participants with symptoms of AR and 106 control subjects without symptoms of AR at the Hitachi Health Care Center, Japan. The habitual consumption of 42 selected nutrients were examined using the brief-type self-administered diet history questionnaire. Faecal samples were collected and subjected to amplicon sequencing of the 16S ribosomal RNA gene hypervariable regions. Association analysis revealed that four nutrients (retinol, vitamin A, cryptoxanthin, and copper) were negatively associated with AR. Among 40 genera examined, relative abundance of Prevotella and Escherichia were associated with AR. Furthermore, significant statistical interactions were observed between retinol and Prevotella. The age- and sex-adjusted odds of AR were 25-fold lower in subjects with high retinol intake and high Prevotella abundance compared to subjects with low retinol intake and low Prevotella abundance. Our data provide insights into complex interplay between dietary nutrients, gut microbiome, and the development of AR.
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Liver tests (LT), especially to measure AST, ALT and GGT levels, are widely used to evaluate the risk of alcohol-related liver disease (ALD). In this study, we investigated the potential genetic ...factors that modulate the association between LTs and alcohol consumption. We conducted a genome-wide interaction meta-analysis in 7856 Japanese subjects from Tohoku Medical Megabank Community-Based Cohort (TMM CommCohort) study recruited in 2013, and identified 2 loci (12q24 and 2p16) with genome-wide significance (P > 5 × 10
). The significant variants in the 12q24 included rs671, a variant associated with alcohol intolerance and located at a coding exon of ALDH2. We found that the amount of alcohol consumption was associated with increased level AST/ALT ratio among the subjects with the rs671 GA genotype. The elevated AST/ALT ratio among subjects with moderate-to-high levels of drinking behavior and the rs671 GA genotype was due to decreased levels of ALT, which was not accompanied with significant differences in AST levels. Although the interaction effect was significant in both men and women, the effect was much larger in men. Our results suggest that the impact of alcohol consumption on LT varies according to the ALDH2 genotype, providing an insight for the accurate screening of ALD in drinkers with the rs671 GA genotype.
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Mosaic loss of chromosome Y (mLOY) in leukocytes has attracted much attention as an emerging biomarker of aging and aging-related diseases. We evaluated the usefulness of saliva for mLOY analysis and ...showed that saliva-derived mLOY is significantly associated with aging and increased physical activity, but not with smoking. While these data support the robust association between saliva-derived mLOY and aging, caution is required when comparing data from saliva-derived and blood-derived mLOY.
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There are ongoing debates on issues relating to returning individual research results (IRRs) and incidental findings (IFs) generated by genetic research in population-based biobanks. To understand ...how to appropriately return genetic results from biobank studies, we surveyed preferences for returning IRRs and IFs among participants of the Tohoku Medical Megabank Project (TMM). We mailed a questionnaire to individuals enrolled in the TMM cohort study (Group 1; n=1031) and a group of Tohoku region residents (Group 2; n=2314). The respondents were required to be over 20 years of age. Nearly 90% of Group 1 participants and over 80% of Group 2 participants expressed a preference for receiving their genetic test results. Furthermore, over 60% of both groups preferred to receive their genetic results 'from a genetic specialist.' A logistic regression analysis revealed that engaging in 'health-conscious behaviors' (such as regular physical activity, having a healthy diet, intentionally reducing alcohol intake and/or smoking and so on) was significant, positively associated with preferring to receive their genetic test results (odds ratio=2.397 (Group 1) and 1.897 (Group 2)). Our findings provided useful information and predictors regarding the return of IRRs and IFs in a population-based biobank.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Formalin‐fixed paraffin‐embedded (FFPE) tissues are promising biological resources for genetic research. Recent improvements in DNA extraction from FFPE samples allowed the use of these tissues for ...multiple sequencing methods. However, fundamental research addressing the application of FFPE‐derived DNA for targeted‐bisulfite sequencing (TB‐seq) is lacking. Here, we evaluated the suitability of FFPE‐derived DNA for TB‐seq. We conducted TB‐seq using FFPE‐derived DNA and corresponding fresh frozen (FF) tissues of patients with kidney cancer and compared the quality of DNA, libraries, and TB‐seq statistics between the two preservation methods. The approximately 600‐bp average fragment size of the FFPE‐derived DNA was significantly shorter than that of the FF‐derived DNA. The sequencing libraries constructed using FFPE‐derived DNA and the mapping ratio were approximately 10 times and 10% lower, respectively, than those constructed using FF‐derived DNA. In the mapped data of FFPE‐derived DNA, duplicated reads accounted for > 60% of the obtained sequence reads, with lower mean on‐target coverage. Therefore, the standard TB‐seq protocol is inadequate for obtaining high‐quality data for epigenetic analysis from FFPE‐derived DNA, and technical improvements are necessary for enabling the use of archived FFPE resources.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Leukocyte telomere length (LTL) and myeloid-derived suppressor cells (MDSC) are associated with aging and the development and progression of cancer. However, the exact nature of this relationship ...remains unclear. Our study aimed to investigate the potential of LTL and MDSC as diagnostic biomarkers for prostate cancer while also seeking to deepen our understanding of the relationship of these potential biomarkers to each other.
Our study involved patients undergoing a prostate biopsy. We analyzed the relative LTL in genomic DNA obtained from peripheral blood leukocytes as well as the percentage of MDSC and their subtypes in peripheral blood mononuclear cells (PBMC). Our evaluation focused on examining the relationship between LTL and MDSC and pathological diagnoses as well as investigating the correlation between LTL and MDSC levels.
In our study of 102 participants, 56 were pathologically diagnosed with localized prostate cancer (cancer group), while 46 tested negative (control group). The cancer group exhibited significantly shorter LTL in comparison to the control group (
= 0.024). Additionally, the cancer group showed a tendency towards a higher percentage of monocytic MDSC (M-MDSC), although this difference did not reach statistical significance (
= 0.056). Our multivariate logistic regression analysis revealed that patients with shorter LTL and higher percentages of M-MDSC had a 2.98-fold (95% CI = 1.001-8.869,
= 0.049) and 3.03-fold (95% CI = 1.152-7.977,
= 0.025) increased risk of prostate cancer diagnosis, respectively. There was also a significant negative correlation between LTL and M-MDSC. (r = -0.347,
< 0.001).
Our research has established a correlation between LTL and MDSC in patients undergoing biopsy for prostate cancer. Notably, we observed that individuals with localized prostate cancer tend to have shorter LTL and a higher percentage of M-MDSC prior to their diagnosis. These findings suggest that LTL and M-MDSC could potentially serve as adjunctive biomarkers for the early diagnosis of prostate cancer.
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