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1.
Clin Genet ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38719617

RESUMEN

Genetic maps are fundamental resources for linkage and association studies. A fine-scale genetic map can be constructed by inferring historical recombination events from the genome-wide structure of linkage disequilibrium-a non-random association of alleles among loci-by using population-scale sequencing data. We constructed a fine-scale genetic map and identified recombination hotspots from 10 092 551 bi-allelic high-quality autosomal markers segregating among 150 unrelated Japanese individuals whose genotypes were determined by high-coverage (30×) whole-genome sequencing, and the genotype quality was carefully controlled by using their parents' and offspring's genotypes. The pedigree information was also utilized for haplotype phasing. The resulting genome-wide recombination rate profiles were concordant with those of the worldwide population on a broad scale, and the resolution was much improved. We identified 9487 recombination hotspots and confirmed the enrichment of previously known motifs in the hotspots. Moreover, we demonstrated that the Japanese genetic map improved the haplotype phasing and genotype imputation accuracy for the Japanese population. The construction of a population-specific genetic map will help make genetics research more accurate.

2.
J Epidemiol ; 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38583947

RESUMEN

BACKGROUND: Genetic epidemiological evidence for the kidney function traits in East Asian population including Japanese remain still relatively unclarified. Especially, the number of GWASs for kidney traits reported still remains limited, and the sample size of each independent study is relatively small. Given the genetic variability between ancestries/ethnicities, implementation of GWAS with sufficiently large sample sizes in specific population of Japanese is considered meaningful. METHODS: We conducted the GWAS meta-analyses of kidney traits by leveraging the GWAS summary data of the representative large genome cohort studies with about 200,000 Japanese participants (n = 202,406 for estimated glomerular filtration rate [eGFR] and n = 200,845 for serum creatinine [SCr]). RESULTS: In the present GWAS meta-analysis, we identified 110 loci with 169 variants significantly associated with eGFR (on chromosomes 1-13 and 15-22; p < 5×10-8), whereas we also identified 112 loci with 176 variants significantly associated with SCr (on chromosomes 1-22; p < 5×10-8), of which one locus (more than 1Mb distant from known loci) with one variant (CD36 rs146148222 on chromosome 7) for SCr was considered as the truly novel finding. CONCLUSIONS: The present GWAS meta-analysis of largest genome cohort studies in Japanese provided some original genomic loci associated with kidney function in Japanese, which may contribute to the possible development of personalized prevention of kidney diseases based on genomic information in the near future.

3.
J Epidemiol ; 2024 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-38403692

RESUMEN

BACKGROUND: The purpose of this study was to report the basic profile of the Miyagi Prefecture part of a repeated center-based survey during the second period (2nd period survey) of the Tohoku Medical Megabank Community-Based Cohort Study (TMM CommCohort Study), as well as the participants' characteristics based on their participation type in the baseline survey. METHODS: The 2nd period survey, conducted from June 2017 to March 2021, included participants of the TMM CommCohort Study (May 2013 to March 2016). In addition to the questionnaire, blood, urine, and physiological function tests were performed during the 2nd period survey. There were three main ways of participation in the baseline survey: Type 1, Type 1 additional, or Type 2 survey. The 2nd period survey was conducted in the same manner as the Type 2 survey, which was based on the community support center (CSC). RESULTS: In Miyagi Prefecture, 29,383 (57.7%) of 50,967 participants participated in the 2nd period survey. The participation rate among individuals who had visited the CSC was approximately 80%. Although some factors differed depending on the participation type in the baseline survey, the 2nd period survey respondents in the Type 1 and Type 2 survey groups at baseline had similar traits. CONCLUSIONS: The 2nd period survey of the TMM CommCohort Study provided detailed follow-up information. Following up on the health conditions of the participants will clarify the long-term effects of disasters and contribute to personalized prevention.

4.
Sci Adv ; 10(4): eade2780, 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38277453

RESUMEN

An East Asian-specific variant on aldehyde dehydrogenase 2 (ALDH2 rs671, G>A) is the major genetic determinant of alcohol consumption. We performed an rs671 genotype-stratified genome-wide association study meta-analysis of alcohol consumption in 175,672 Japanese individuals to explore gene-gene interactions with rs671 behind drinking behavior. The analysis identified three genome-wide significant loci (GCKR, KLB, and ADH1B) in wild-type homozygotes and six (GCKR, ADH1B, ALDH1B1, ALDH1A1, ALDH2, and GOT2) in heterozygotes, with five showing genome-wide significant interaction with rs671. Genetic correlation analyses revealed ancestry-specific genetic architecture in heterozygotes. Of the discovered loci, four (GCKR, ADH1B, ALDH1A1, and ALDH2) were suggested to interact with rs671 in the risk of esophageal cancer, a representative alcohol-related disease. Our results identify the genotype-specific genetic architecture of alcohol consumption and reveal its potential impact on alcohol-related disease risk.


Asunto(s)
Pueblos del Este de Asia , Neoplasias Esofágicas , Estudio de Asociación del Genoma Completo , Humanos , Polimorfismo de Nucleótido Simple , Consumo de Bebidas Alcohólicas/genética , Genotipo , Aldehído Deshidrogenasa Mitocondrial/genética , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/genética , Predisposición Genética a la Enfermedad
5.
J Atheroscler Thromb ; 30(12): 1950-1965, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37813642

RESUMEN

AIM: The influence of family history of diabetes, probably reflecting genetic and lifestyle factors, on the association of combined genetic and lifestyle risks with diabetes is unknown. We examined these associations. METHODS: This cross-sectional study included 9,681 participants in the Tohoku Medical Megabank Community-based Cohort Study. A lifestyle score, which was categorized into ideal, intermediate, and poor lifestyles, was given. Family history was obtained through a self-reported questionnaire. A polygenic risk score (PRS) was constructed in the target data (n=1,936) using publicly available genome-wide association study summary statistics from BioBank Japan. For test data (n=7,745), we evaluated PRS performance and examined the associations of combined family history and genetic and lifestyle risks with diabetes. Diabetes was defined as non-fasting blood glucose ≥ 200 mmHg, HbA1c ≥ 6.5%, and/or self-reported diabetes treatment. RESULTS: In test data, 467 (6.0%) participants had diabetes. Compared with a low genetic risk and an ideal lifestyle without a family history, the odds ratio (OR) was 3.73 (95% confidence interval [CI], 1.92-7.00) for a lower genetic risk and a poor lifestyle without a family history. Family history was significantly associated with diabetes (OR, 3.58 [95% CI, 1.73-6.98]), even in those with a low genetic risk and an ideal lifestyle. Even among participants who had an ideal lifestyle without a family history, a high genetic risk was associated with diabetes (OR, 2.49 [95% CI, 1.65-3.85]). Adding PRS to family history and conventional lifestyle risk factors improved the prediction ability for diabetes. CONCLUSIONS: Our findings support the notion that a healthy lifestyle is important to prevent diabetes regardless of genetic risk.


Asunto(s)
Diabetes Mellitus , Estudio de Asociación del Genoma Completo , Humanos , Estudios de Cohortes , Estudios Transversales , Predisposición Genética a la Enfermedad , Diabetes Mellitus/epidemiología , Diabetes Mellitus/genética , Factores de Riesgo , Estilo de Vida
6.
J Alzheimers Dis ; 95(4): 1469-1480, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37718802

RESUMEN

BACKGROUND: Olfactory function decline has recently been reported to be associated with a risk of cognitive impairment. Few population-based studies have included younger adults when examining the association between olfactory test data with multiple odor intensities and suspected cognitive impairment. OBJECTIVE: We investigated the association between high-resolution olfactory test data with fewer odors and suspected cognitive impairments. We also examined the differences between older and younger adults in this association. METHODS: The Japanese version of the Montreal Cognitive Assessment (MoCA-J) was administered to 1,450 participants, with three odor-intensity-level olfactometry using six different odors. Logistic regressions to discriminate suspected cognitive impairment were conducted to examine the association, adjusted for age, sex, education duration, and smoking history. Data were collected from the Program by Tohoku University Tohoku Medical Megabank Organization, with an additional olfactory test conducted between 2019 and 2021. RESULTS: We generally observed that the lower the limit of distinguishable odor intensity was, the higher the MoCA-J score was. The combination of spearmint and stuffy socks contributed most to the distinction between suspected and unsuspected cognitive impairment. Furthermore, the association was significant in women aged 60-74 years (adjusted odds ratio 0.881, 95% confidence interval [0.790, 0.983], p = 0.024). CONCLUSIONS: The results indicate an association between the limit of distinguishable odor intensity and cognitive function. The olfactory test with multiple odor intensity levels using fewer odors may be applicable for the early detection of mild cognitive impairment, especially in older women aged 60-74 years.

7.
Respir Investig ; 61(5): 588-600, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37429072

RESUMEN

BACKGROUND: Birth weight, as a measure of intrauterine growth, is commonly used in epidemiological studies and is reported to be associated with adult lung function. However, findings regarding this association in previous studies have been inconsistent. Furthermore, no studies have reported associations stratified by age or smoking status, or adjusted for eosinophil count or other parameters related to type 2 airway inflammation. METHODS: This cross-sectional study included 2632 men and 7237 women aged ≥20 years living in Miyagi Prefecture, Japan. Lung function was assessed based on spirometry. Birth weight data were obtained through a questionnaire survey. Analysis of covariance was used to evaluate the associations between birth weight and lung function, adjusting for potential confounders. Stratified analyses by age and smoking status were also conducted, together with a sub-analysis for low birth-weight participants. RESULTS: Birth weight was positively associated with forced expiratory volume in 1 s (FEV1) for both sexes and with vital capacity in women, after adjusting for height, age, smoking status, and parameters related to type 2 airway inflammation. The stratified analysis for smoking status revealed associations in never-smokers and ex-smokers. When stratified by age, the associations were confirmed in middle-aged participants. The effect of smoking status on the FEV1 of low birth-weight participants was not significant. CONCLUSIONS: Our analysis of a large, Japanese adult population showed that birth weight was independently and positively associated with adult lung function, even after adjustment for age, height, smoking status, and parameters related to type 2 airway inflammation.


Asunto(s)
Pulmón , Fumar , Masculino , Persona de Mediana Edad , Humanos , Adulto , Femenino , Estudios de Cohortes , Peso al Nacer , Fumar/epidemiología , Estudios Transversales , Pueblos del Este de Asia , Volumen Espiratorio Forzado , Capacidad Vital , Espirometría , Inflamación
9.
Sci Rep ; 13(1): 7052, 2023 04 29.
Artículo en Inglés | MEDLINE | ID: mdl-37120602

RESUMEN

Observational studies suggest that abnormal glucose metabolism and insulin resistance contribute to colorectal cancer; however, the causal association remains unknown, particularly in Asian populations. A two-sample Mendelian randomisation analysis was performed to determine the causal association between genetic variants associated with elevated fasting glucose, haemoglobin A1c (HbA1c), and fasting C-peptide and colorectal cancer risk. In the single nucleotide polymorphism (SNP)-exposure analysis, we meta-analysed study-level genome-wide associations of fasting glucose (~ 17,289 individuals), HbA1c (~ 52,802 individuals), and fasting C-peptide (1,666 individuals) levels from the Japanese Consortium of Genetic Epidemiology studies. The odds ratios of colorectal cancer were 1.01 (95% confidence interval [CI], 0.99-1.04, P = 0.34) for fasting glucose (per 1 mg/dL increment), 1.02 (95% CI, 0.60-1.73, P = 0.95) for HbA1c (per 1% increment), and 1.47 (95% CI, 0.97-2.24, P = 0.06) for fasting C-peptide (per 1 log increment). Sensitivity analyses, including Mendelian randomisation-Egger and weighted-median approaches, revealed no significant association between glycaemic characteristics and colorectal cancer (P > 0.20). In this study, genetically predicted glycaemic characteristics were not significantly related to colorectal cancer risk. The potential association between insulin resistance and colorectal cancer should be validated in further studies.


Asunto(s)
Neoplasias Colorrectales , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Factores de Riesgo , Hemoglobina Glucada/genética , Resistencia a la Insulina/genética , Péptido C , Pueblos del Este de Asia , Glucemia/metabolismo , Glucosa , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/complicaciones , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Estudio de Asociación del Genoma Completo
10.
Hypertens Res ; 46(5): 1247-1256, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36806793

RESUMEN

People who experience natural disasters have a high risk of developing cardiovascular diseases. We investigated the association between the extent of house collapse and urine sodium-to-potassium (UNa/K) ratio of 2011 Great East Japan Earthquake victims. We used the baseline survey data of the Tohoku Medical Megabank Project Community-Based Cohort Study of 29 542 individuals (aged 20-74 years) residing in the affected areas. The UNa/K ratio was calculated using spot urinary electrolyte values. Analysis of covariance was used to calculate the multivariate-adjusted geometric means of the UNa/K ratio in the following groups stratified according to the self-reported extent of house collapse: total collapse (TC), half collapse (HC), partial collapse (PC), and no damage (ND). Multivariable-adjusted odds ratios (ORs) for a high UNa/K ratio were calculated using logistic regression. The TC, HC, PC, and ND groups comprised 5 359 (18.1%), 3 576 (12.1%), 7 331 (24.8%), and 13 276 (44.9%) participants, respectively. The TC (3.33; 95% confidence interval [CI], 3.28-3.38), HC (3.37; 3.30-3.43), and PC (3.32; 3.28-3.37) groups had significantly higher multivariate-adjusted geometric means of the UNa/K ratio than the ND (3.24; 3.21-3.27) group. The multivariable-adjusted ORs (95% CIs) for a high UNa/K ratio in the TC, HC, and PC groups vs. the ND group were 1.07 (0.99-1.15), 1.20 (1.11-1.31), and 1.20 (1.12-1.28), respectively. Similar associations between house collapse and UNa/K ratio were observed for both sexes. We report that victims of a natural disaster tend to have a diet with high sodium-to-potassium ratio.


Asunto(s)
Terremotos , Choque , Masculino , Femenino , Humanos , Tsunamis , Estudios Transversales , Estudios de Cohortes , Japón , Sodio , Potasio
11.
J Hum Genet ; 68(2): 55-64, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36404353

RESUMEN

Chronic kidney disease (CKD) is a syndrome characterized by a gradual loss of kidney function with decreased estimated glomerular filtration rate (eGFR), which may be accompanied by an increase in the urine albumin-to-creatinine ratio (UACR). Although trans-ethnic genome-wide association studies (GWASs) have been conducted for kidney-related traits, there have been few analyses in the Japanese population, especially for the UACR trait. In this study, we conducted a GWAS to identify loci related to multiple kidney-related traits in Japanese individuals. First, to detect loci associated with CKD, eGFR, and UACR, we performed separate GWASs with the following two datasets: 475 cases of CKD diagnosed at seven university hospitals and 3471 healthy subjects (dataset 1) and 3664 cases of CKD-suspected individuals with eGFR <60 ml/min/1.73 m2 or urinary protein ≥ 1+ and 5952 healthy subjects (dataset 2). Second, we performed a meta-analysis between these two datasets and detected the following associated loci: 10 loci for CKD, 9 loci for eGFR, and 22 loci for UACR. Among the loci detected, 22 have never been reported previously. Half of the significant loci for CKD were shared with those for eGFR, whereas most of the loci associated with UACR were different from those associated with CKD or eGFR. The GWAS of the Japanese population identified novel genetic components that were not previously detected. The results also suggest that the group primarily characterized by increased UACR possessed genetically different features from the group characterized by decreased eGFR.


Asunto(s)
Estudio de Asociación del Genoma Completo , Insuficiencia Renal Crónica , Humanos , Bancos de Muestras Biológicas , Pueblos del Este de Asia , Albuminuria/orina , Creatinina/orina , Riñón , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/genética , Tasa de Filtración Glomerular/genética
12.
Am J Ophthalmol ; 245: 193-201, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36162535

RESUMEN

PURPOSE: A meta-analysis suggests a relationship between abnormal glucose metabolism and primary open-angle glaucoma (POAG); however, the causal association between them remains controversial. We therefore conducted a Mendelian randomization (MR) study to assess the causal association between genetically predicted glycemic traits and the risk of POAG. DESIGN: Two-sample MR design. METHODS: We examined the genetically predicted measures of fasting glucose, hemoglobin A1c (HbA1c), and fasting C-peptide, in relation to POAG. For the single nucleotide polymorphism (SNP)-exposure analyses, we meta-analyzed the study-level genome-wide associations of fasting glucose levels (n = 17,289; n of SNPs = 34), HbA1c (n = 52,802; n of SNPs = 43), and fasting C-peptide levels (n=1666; n of SNPs = 17) from the Japanese Consortium of Genetic Epidemiology studies. We used summary statistics from the BioBank Japan projects (n = 3980 POAG cases and 18,815 controls) for the SNP-outcome association. RESULTS: We observed no association of genetically predicted HbA1c and fasting C-peptide with POAG. The MR inverse-variance-weighted (IVW) odds ratios (ORs) were 1.44 (95% confidence interval [CI], 0.78-2.65; P = .25) for HbA1c (per 1% increment) and 0.92 (95% CI, 0.56-1.53; P = .76) for fasting C-peptide (per 2-fold increment). A significant association between fasting glucose (per 10 mg/dL-increment) and POAG was observed according to the MR IVW analysis (OR = 1.48 [95% CI, 1.10-1.79, P = .009]); however, sensitivity analyses, including MR-Egger and weighted-median methods, did not support this association (P > .10). CONCLUSIONS: We did not observe strong evidence to support the association between genetically predicted glycemic traits and POAG in the Japanese population.


Asunto(s)
Glaucoma de Ángulo Abierto , Análisis de la Aleatorización Mendeliana , Humanos , Hemoglobina Glucada , Estudio de Asociación del Genoma Completo/métodos , Péptido C/genética , Pueblos del Este de Asia , Glaucoma de Ángulo Abierto/genética , Factores de Riesgo , Polimorfismo de Nucleótido Simple , Glucosa
13.
Genome Biol ; 23(1): 268, 2022 12 27.
Artículo en Inglés | MEDLINE | ID: mdl-36575460

RESUMEN

BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.


Asunto(s)
Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Caracteres Sexuales , Fenotipo , Lípidos/genética , Polimorfismo de Nucleótido Simple , Pleiotropía Genética
14.
Sci Rep ; 12(1): 17656, 2022 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-36271231

RESUMEN

Development of methods for population screening is necessary to improve the efficiency of secondary prevention of diseases. Until now, a common cutoff has been used for all people in the data set. However, if big data for health information can be used to modify individual cutoffs according to background factors, it may avoid wasting medical resources. Here we show that the estimated prevalence of the Center for Epidemiologic Studies Depression Scale positivity can be visualized by a heatmap using background factors from epidemiological big data and scores from the Athens Insomnia Scale. We also show that cutoffs based on the estimated prevalence can be used to decrease the number of people screened without decreasing the number of prevalent cases detected. Since this method can be applied to the screening of different outcomes, we believe our work can contribute to the development of efficient screening methods for various diseases.


Asunto(s)
Depresión , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Prevalencia , Depresión/epidemiología , Depresión/diagnóstico , Tamizaje Masivo/métodos
15.
Cancer Prev Res (Phila) ; 15(12): 827-836, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36040498

RESUMEN

The associations between blood lipids, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides, and low-density lipoprotein cholesterol (LDL-C), and colorectal cancer risk are controversial. We evaluated potential causal relationships between blood lipids and colorectal cancer risk. Using the baseline data from the Japanese Consortium of Genetic Epidemiology studies, we estimated the single-nucleotide polymorphism (SNP)-exposure associations (n = 34,546 for TC, n = 50,290 for HDL-C, n = 51,307 for triglycerides, and n = 30,305 for LDL-C). We also estimated the SNP-outcome associations in another Japanese dataset (n = 7,936 colorectal cancer cases and n = 38,042 controls). We conducted Mendelian randomization (MR) analyses for the association between each blood lipid type and the risk of colorectal cancer using an inverse variance-weighted method. The total variances explained by the selected SNPs in TC (68 SNPs), HDL-C (50 SNPs), log-transformed triglycerides (26 SNPs), and LDL-C (35 SNPs) were 7.0%, 10.0%, 6.2%, and 5.7%, respectively. The odds ratios for colorectal cancer were 1.15 [95% confidence interval (CI), 1.01-1.32] per 1 standard deviation (SD; 33.3 mg/dL) increase in TC, 1.11 (95% CI, 0.98-1.26) per 1 SD (15.4 mg/dL) increase in HDL-C, 1.06 (95% CI, 0.90-1.26) per 1 SD (0.5 log-mg/dL) increase in log-transformed triglycerides, and 1.17 (95% CI, 0.91-1.50) per 1 SD (29.6 mg/dL) increase in LDL-C. Sensitivity analyses consistently suggested the positive association between TC and colorectal cancer, whereas results of each lipid component were inconsistent. In conclusion, this large MR study of a Japanese population showed a potentially causal association between high TC and colorectal cancer risk, although the association between each lipid component and colorectal cancer remained inconclusive. PREVENTION RELEVANCE: In this large MR analysis of a Japanese population, a positive association was found between genetically predicted high total cholesterol (TC) levels and an increased risk of colorectal cancer. Therefore, lowering TC levels by lifestyle modifications or medications may be justified for the purpose of preventing colorectal cancer.


Asunto(s)
Neoplasias Colorrectales , Análisis de la Aleatorización Mendeliana , Humanos , LDL-Colesterol/genética , Epidemiología Molecular , Japón/epidemiología , Factores de Riesgo , HDL-Colesterol/genética , Triglicéridos/genética , Lípidos , Polimorfismo de Nucleótido Simple , Estudio de Asociación del Genoma Completo , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética
16.
Am J Hum Genet ; 109(8): 1366-1387, 2022 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-35931049

RESUMEN

A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.


Asunto(s)
Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Cromatina/genética , Genómica , Humanos , Lípidos/genética , Polimorfismo de Nucleótido Simple/genética
17.
Eur J Clin Nutr ; 76(8): 1103-1110, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35132194

RESUMEN

BACKGROUND/OBJECTIVES: Low-carbohydrate diets (LCD) are useful for weight reduction, and 50-55% carbohydrate consumption is associated with minimal risk. Genetic differences were related to nutritional consumption, food preferences, and dietary patterns, but whether particular genetic differences in individuals influence LCD adherence is unknown. SUBJECTS/METHODS: We conducted a GWAS on adherence to LCD utilizing 14,076 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a previously validated semiquantitative food frequency questionnaire to estimate food consumption. Association of the imputed variants with the LCD score by Halton et al. we used linear regression analysis adjusting for sex, age, total dietary energy consumption, and components 1 to 10 by principal component analysis. We repeated the analysis with adjustment for alcohol consumption (g/day) in addition to the above-described variables. RESULTS: Men and women combined analysis without adjustment for alcohol consumption; we found 395 variants on chromosome 12 associated with the LCD score having P values <5 × 10-8. A conditional analysis with the addition of the dosage data of rs671 on chromosome 12 as a covariate, P values for all 395 SNPs on chromosome 12 turned out to be insignificant. In the analysis with additional adjustment for alcohol consumption, we did not identify any SNPs associated with the LCD score. CONCLUSION: We found rs671 was inversely associated with adherence to LCD, but that was strongly confounded by alcohol consumption.


Asunto(s)
Dieta Baja en Carbohidratos , Estudio de Asociación del Genoma Completo , Estudios de Cohortes , Femenino , Humanos , Japón , Masculino , Riesgo
18.
Hypertens Res ; 45(5): 866-875, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35043014

RESUMEN

The sodium-to-potassium (Na/K) ratio is known to be associated with blood pressure (BP). However, no reference value has been established since the urinary Na/K (uNa/K) ratio is known to have diurnal and day-to-day variations. Therefore, we investigated the number of days required to yield a better association between the morning uNa/K ratio and home BP (HBP) and determined a morning uNa/K ratio value that can be used as a reference value in participants who are not taking antihypertensive medication. This was a cross-sectional study using data from the Tohoku Medical Megabank Project Cohort Study. A total of 3122 participants borrowed HBP and uNa/K ratio monitors for 10 consecutive days. We assessed the relationship between the morning uNa/K ratio from 1 day to 10 days and home hypertension (HBP ≥ 135/85 mmHg) using multiple logistic regression models. Although a 1-day measurement of the morning uNa/K ratio was positively associated with home hypertension, multiple measurements of the morning uNa/K ratio were strongly related to home hypertension. The average morning uNa/K ratio was relatively stable after 3 days (adjusted odds ratio of home hypertension per unit increase in the uNa/K ratio for more than 3 days: 1.19-1.23). In conclusion, there was no threshold for the uNa/K ratio, and the morning uNa/K ratio was linearly associated with home hypertension. The Na/K ratio 2.0 calculated from the Dietary Reference Intakes for Japanese might be a good indication. Regarding the stability of the association between the morning uNa/K ratio and BP, more than 3 days of measurements is desirable.


Asunto(s)
Hipertensión , Potasio , Presión Sanguínea , Estudios de Cohortes , Estudios Transversales , Humanos , Hipertensión/epidemiología , Prevalencia , Valores de Referencia , Sodio
19.
Disaster Med Public Health Prep ; 16(5): 1966-1974, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-34414879

RESUMEN

OBJECTIVE: This study aims to evaluate the long-term impact of living in postdisaster prefabricated temporary housing on social interaction activities and mental health status. METHODS: A total of 917 adult residents in a coastal town, whose residences were destroyed by the tsunami caused by the Great East Japan Earthquake (GEJE), were enrolled for the assessment held 5 y after the disaster. They answered questions about their experience and consequence of living in prefabricated temporary housing after the disaster. Their present scores on 5 types of self-reported measures regarding the psychosocial or psychiatric status and their present and recalled social interaction activities were cross-sectionally collected. RESULTS: A total of 587 (64.0%) participants had a history of living in prefabricated temporary housing, while the other 330 (36.0%) had not. The prevalence of social interaction activities significantly decreased after the GEJE. However, the experience of living in prefabricated temporary housing did not adversely affect the subsequent social interaction activities or mental conditions of the participants 5 y after the disaster. CONCLUSIONS: Living in postdisaster prefabricated temporary housing may not negatively impact subsequent psychosocial conditions or social interaction activities 5 y later.


Asunto(s)
Desastres , Terremotos , Adulto , Humanos , Vivienda , Estrés Psicológico/epidemiología , Tsunamis , Japón/epidemiología
20.
J Epidemiol ; 32(5): 221-227, 2022 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-33390464

RESUMEN

BACKGROUND: Alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) are enzymes associated with diabetes mellitus (DM) prevalence. However, limited information is available regarding the association of liver enzymes and DM consistently present in obese and non-obese individuals. We examined whether the combination of ALT and GGT enzymes is associated with the prevalence of DM, regardless of obesity, in a general Japanese population. METHODS: We conducted a cross-sectional study of 62,786 participants aged ≥20 years who lived in Miyagi and Iwate, Japan. We divided all the participants into eight groups according to the ALT level (low: <30 IU/L and high: ≥30 IU/L), GGT level (low: <50 IU/L and high: ≥50 IU/L), and the presence of obesity. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression analysis, adjusting for potential confounders, to determine associations of the combination of ALT and GGT levels and obesity with DM prevalence. RESULTS: Overall, 6,008 participants (9.6%) had DM. Compared to non-obese individuals with low ALT and GGT levels, the participants with high ALT and GGT levels had high ORs for DM in both obese (OR 4.06; 95% CI, 3.61-4.56) and non-obese groups (OR 2.19; 95% CI, 1.89-2.52). The obese group had high ORs for DM, even at low ALT and GGT levels. CONCLUSION: High ALT and GGT levels are associated with DM prevalence in obese and non-obese participants. This finding suggests that correcting ALT and GGT levels and controlling obesity are important for the prevention of DM.


Asunto(s)
Alanina Transaminasa/sangre , Diabetes Mellitus , Obesidad , gamma-Glutamiltransferasa/sangre , Estudios de Cohortes , Estudios Transversales , Diabetes Mellitus/sangre , Diabetes Mellitus/epidemiología , Humanos , Hígado , Obesidad/sangre , Obesidad/epidemiología
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