A genome-wide association study based on the China Kadoorie Biobank identifies genetic associations between snoring and cardiometabolic traits

Despite the high prevalence of snoring in Asia, little is known about the genetic etiology of snoring and its causal relationships with cardiometabolic traits. Based on 100,626 Chinese individuals, a genome-wide association study on snoring was conducted. Four novel loci were identified for snoring traits mapped on SLC25A21, the intergenic region of WDR11 and FGFR, NAA25, ALDH2, and VTI1A, respectively. The novel loci highlighted the roles of structural abnormality of the upper airway and craniofacial region and dysfunction of metabolic and transport systems in the development of snoring. In the two-sample bi-directional Mendelian randomization analysis, higher body mass index, weight, and elevated blood pressure were causal for snoring, and a reverse causal effect was observed between snoring and diastolic blood pressure. Altogether, our results revealed the possible etiology of snoring in China and indicated that managing cardiometabolic health was essential to snoring prevention, and hypertension should be considered among snorers

Association of DNA Methylation at \u3cem\u3eCPT1A\u3c/em\u3e Locus with Metabolic Syndrome in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study

In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ~470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models. A Bonferroni-corrected P-value of 1.1 x 10−7 was considered significant. Methylation at two CpG sites in CPT1A on chromosome 11 was significantly associated with MetS (P for cg00574958 = 2.6x10-14 and P for cg17058475 = 1.2x10-9). Significant associations were replicated in both European and African ancestry participants of the Bogalusa Heart Study. Our findings suggest that methylation in CPT1A is a promising epigenetic marker for MetS risk which could become useful as a treatment target in the future

The Changes of Nutrition Labeling of Packaged Food in Hangzhou in China during 2008∼2010

OBJECTIVE: To understand the changes of the nutrition labeling of packaged food in China two years after the promulgation of the Regulation for Food Nutrition Labeling, which encourages food manufacturers to identify nutrition labeling. METHODS: Investigators copied out the nutrition information panel, nutrition claim and nutrient function claim of packaged food in a supermarket with prepared questionnaire and finished normative judgment in 2008 and 2010. RESULTS: 4693 and 5526 kinds of packaged food were investigated separately. Nutrition information panel, nutrition claim and nutrient function claim were found on the food label of 27.6%, 13.0% and 1.9% of packaged food respectively in 2008, while 35.1%, 7.7% and 2.3% in 2010. The nutrition information panel which labeled energy, protein, fat, carbohydrate and sodium was 597 (43.8%) and 1661 (85.9%) in 2008 and 2010, only 134 (9.8%) and 985 (51.0%) nutrition information panel were totally normalized. Nutrition claim and nutrient function claim focused on vitamin, mineral and dietary fiber. The total qualified proportions for nutrition claim were increased significantly for most of the nutrients, except for cholesterol. There were 6 (6.4%) and 5 (3.9%) nutrient function claims with hinting of therapeutic effects on diseases separately. CONCLUSION: Although the voluntary regulation remarkably improved the level of normalization for nutrition labeling, its role on the prevalence was minus. It's imperative to enforce nutrition labeling for not only China but also other countries, and furthermore, health education on nutrition labeling should be initiated to support the policy

DNA methylation-based estimator of telomere length

Telomere length (TL) is associated with several aging-related diseases. Here, we present a DNA methylation estimator of TL (DNAmTL) based on 140 CpGs. Leukocyte DNAmTL is applicable across the entire age spectrum and is more strongly associated with age than measured leukocyte TL (LTL) (r ~-0.75 for DNAmTL versus r ~ -0.35 for LTL). Leukocyte DNAmTL outperforms LTL in predicting: i) time-to-death (p=2.5E-20), ii) time-to-coronary heart disease (p=6.6E-5), iii) time-to-congestive heart failure (p=3.5E-6), and iv) association with smoking history (p=1.21E-17). These associations are further validated in large scale methylation data (n=10k samples) from the Framingham Heart Study, Women's Health Initiative, Jackson Heart Study, InChianti, Lothian Birth Cohorts, Twins UK, and Bogalusa Heart Study. Leukocyte DNAmTL is also associated with measures of physical fitness/functioning (p=0.029), age-at-menopause (p=0.039), dietary variables (omega 3, fish, vegetable intake), educational attainment (p=3.3E-8) and income (p=3.1E-5). Experiments in cultured somatic cells show that DNAmTL dynamics reflect in part cell replication rather than TL per se. DNAmTL is not only an epigenetic biomarker of replicative history of cells, but a useful marker of age-related pathologies that are associated with it

Quality of dietary fat and genetic risk of type 2 diabetes: individual participant data meta-analysis.

OBJECTIVE: To investigate whether the genetic burden of type 2 diabetes modifies the association between the quality of dietary fat and the incidence of type 2 diabetes. DESIGN: Individual participant data meta-analysis. DATA SOURCES: Eligible prospective cohort studies were systematically sourced from studies published between January 1970 and February 2017 through electronic searches in major medical databases (Medline, Embase, and Scopus) and discussion with investigators. REVIEW METHODS: Data from cohort studies or multicohort consortia with available genome-wide genetic data and information about the quality of dietary fat and the incidence of type 2 diabetes in participants of European descent was sought. Prospective cohorts that had accrued five or more years of follow-up were included. The type 2 diabetes genetic risk profile was characterized by a 68-variant polygenic risk score weighted by published effect sizes. Diet was recorded by using validated cohort-specific dietary assessment tools. Outcome measures were summary adjusted hazard ratios of incident type 2 diabetes for polygenic risk score, isocaloric replacement of carbohydrate (refined starch and sugars) with types of fat, and the interaction of types of fat with polygenic risk score. RESULTS: Of 102 305 participants from 15 prospective cohort studies, 20 015 type 2 diabetes cases were documented after a median follow-up of 12 years (interquartile range 9.4-14.2). The hazard ratio of type 2 diabetes per increment of 10 risk alleles in the polygenic risk score was 1.64 (95% confidence interval 1.54 to 1.75, I2=7.1%, τ2=0.003). The increase of polyunsaturated fat and total omega 6 polyunsaturated fat intake in place of carbohydrate was associated with a lower risk of type 2 diabetes, with hazard ratios of 0.90 (0.82 to 0.98, I2=18.0%, τ2=0.006; per 5% of energy) and 0.99 (0.97 to 1.00, I2=58.8%, τ2=0.001; per increment of 1 g/d), respectively. Increasing monounsaturated fat in place of carbohydrate was associated with a higher risk of type 2 diabetes (hazard ratio 1.10, 95% confidence interval 1.01 to 1.19, I2=25.9%, τ2=0.006; per 5% of energy). Evidence of small study effects was detected for the overall association of polyunsaturated fat with the risk of type 2 diabetes, but not for the omega 6 polyunsaturated fat and monounsaturated fat associations. Significant interactions between dietary fat and polygenic risk score on the risk of type 2 diabetes (P>0.05 for interaction) were not observed. CONCLUSIONS: These data indicate that genetic burden and the quality of dietary fat are each associated with the incidence of type 2 diabetes. The findings do not support tailoring recommendations on the quality of dietary fat to individual type 2 diabetes genetic risk profiles for the primary prevention of type 2 diabetes, and suggest that dietary fat is associated with the risk of type 2 diabetes across the spectrum of type 2 diabetes genetic risk.The EPIC-InterAct study received funding from the European Union (Integrated Project LSHM-CT-2006-037197 in the Framework Programme 6 of the European Community). We thank all EPIC participants and staff for their contribution to the study. We thank Nicola Kerrison (MRC Epidemiology Unit, University of Cambridge, Cambridge, UK) for managing the data for the InterAct Project. In addition, InterAct investigators acknowledge funding from the following agencies: MT: Health Research Fund (FIS) of the Spanish Ministry of Health; the CIBER en Epidemiología y Salud Pública (CIBERESP), Spain; Murcia Regional Government (N° 6236); JS: JS was supported by a Heisenberg-Professorship (SP716/2-1), a Clinical Research Group (KFO218/1) and a research group (Molecular Nutrition to JS) of the Bundesministerium für Bildung und Forschung (BMBF); YTvdS, JWJB, PHP, IS: Verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht; HBBdM: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); MDCL: Health Research Fund (FIS) of the Spanish Ministry of Health; Murcia Regional Government (N° 6236); FLC: Cancer Research UK; PD: Wellcome Trust; LG: Swedish Research Council; GH: The county of Västerbotten; RK: Deutsche Krebshilfe; TJK: Cancer Research UK; KK: Medical Research Council UK, Cancer Research UK; AK: Medical Research Council (Cambridge Lipidomics Biomarker Research Initiative); CN: Health Research Fund (FIS) of the Spanish Ministry of Health; Murcia Regional Government (N° 6236); KO: Danish Cancer Society; OP: Faculty of Health Science, 47 University of Aarhus, Denmark; JRQ: Asturias Regional Government; LRS: Asturias Regional Government; AT: Danish Cancer Society; RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government; DLvdA, WMMV: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); MMC: Wellcome Trust (083270/Z/07/Z), MRC (G0601261)

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.Peer reviewe

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.</p

Uric acid is associated with metabolic syndrome in children and adults in a community: the Bogalusa Heart Study.

Elevated serum uric acid (UA) is commonly found in subjects with metabolic syndrome (MetS). This study examined the association of UA with levels of individual MetS components and the degree of their clustering patterns in both children and adults.The study sample consisted of 2614 children aged 4-18 years and 2447 adults aged 19-54 years. MetS components included body mass index (BMI), mean arterial pressure (MAP), triglycerides to high-density lipoprotein cholesterol ratio (TG/HDLC), and homeostasis model assessment of insulin resistance (HOMA). Observed/expected (O/E) ratio and intra-class correlation coefficient (ICC) were used as a measure of the degree of clustering of categorical and continuous MetS variables, respectively.UA was positively and significantly associated only with BMI in children but with all four components in adults. The odds ratio for MetS associated with 1 mg/dL increase of UA was 1.74 (p<0.001) in children and 1.92 (p<0.001) in adults. O/E ratios showed a significant, increasing trend with increasing UA quartiles in both children and adults for 3- and 4-variable clusters with p-values for trend <0.001, except for BMI-MAP-TG/HDLC and MAP-TG/HDLC-HOMA clusters in children and MAP-TG/HDLC-HOMA cluster in adults. ICCs of 3 and 4 components increased with increasing UA quartiles in children and adults.These results indicate that UA may play a role in the development of MetS in both pediatric and adult populations alike, which may aid in the identification and treatment of high risk individuals for MetS and related clinical disorders in early life

Associations between experience of stressful life events and cancer prevalence in China: results from the China Kadoorie Biobank study

Abstract Background Studies examining the relationships of stressful life events and cancer yielded inconsistent findings, while relevant evidence in mainland China is scarce. The current study sought to determine whether experience of stressful life events was associated with cancer prevalence in Chinese population. Methods We used cross-sectional data from the China Kadoorie Biobank study which that recruited 0.5 million Chinese adults aged 30 to 79 from 2004 to 2008. Logistic regression models were used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for cancer associated with stressful life events reported at baseline. Results Among the 461,696 participants included in this analysis, 2,122 (0.46%) had self-reported cancer with the mean (SD) age was 57.12 (9.71) years. Compared to those without any stressful life event, participants who experienced 1 and 2 or more events had significantly higher odds of cancer, with the ORs of 1.80 (95% CI: 1.58–2.05) and 3.05 (2.18–4.28). For categories of work-, family-, and personal-related events, the OR of cancer was 1.48 (1.07–2.05), 2.06 (1.80–2.35), and 1.65 (1.17–2.33), respectively. Regarding the specific stressful life events, loss of income/living on debt, major conflict within family, death/major illness of other close family member, and major injury/traffic accident were significantly associated with increased odds of cancer, with the ORs of 2.64 (1.81–3.86), 1.73 (1.20–2.50), 2.36 (2.05–2.72), and 2.11 (1.43–3.13). Conclusion Our findings suggested that experiences of cumulative and specific stressful life events were significantly associated with increased cancer prevalence in Chinese population