Performing genetic studies in multiple human populations can identify disease risk alleles that are common in one population but rare in others, with the potential to illuminate pathophysiology, ...health disparities, and the population genetic origins of disease alleles. Here we analysed 9.2 million single nucleotide polymorphisms (SNPs) in each of 8,214 Mexicans and other Latin Americans: 3,848 with type 2 diabetes and 4,366 non-diabetic controls. In addition to replicating previous findings, we identified a novel locus associated with type 2 diabetes at genome-wide significance spanning the solute carriers SLC16A11 and SLC16A13 (P = 3.9 × 10(-13); odds ratio (OR) = 1.29). The association was stronger in younger, leaner people with type 2 diabetes, and replicated in independent samples (P = 1.1 × 10(-4); OR = 1.20). The risk haplotype carries four amino acid substitutions, all in SLC16A11; it is present at ~50% frequency in Native American samples and ~10% in east Asian, but is rare in European and African samples. Analysis of an archaic genome sequence indicated that the risk haplotype introgressed into modern humans via admixture with Neanderthals. The SLC16A11 messenger RNA is expressed in liver, and V5-tagged SLC16A11 protein localizes to the endoplasmic reticulum. Expression of SLC16A11 in heterologous cells alters lipid metabolism, most notably causing an increase in intracellular triacylglycerol levels. Despite type 2 diabetes having been well studied by genome-wide association studies in other populations, analysis in Mexican and Latin American individuals identified SLC16A11 as a novel candidate gene for type 2 diabetes with a possible role in triacylglycerol metabolism.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is a lack of multi-session P300 datasets for Brain-Computer Interfaces (BCI). Publicly available datasets are usually limited by small number of participants with few BCI sessions. In this ...sense, the lack of large, comprehensive datasets with various individuals and multiple sessions has limited advances in the development of more effective data processing and analysis methods for BCI systems. This is particularly evident to explore the feasibility of deep learning methods that require large datasets. Here we present the BCIAUT-P300 dataset, containing 15 autism spectrum disorder individuals undergoing 7 sessions of P300-based BCI joint-attention training, for a total of 105 sessions. The dataset was used for the 2019 IFMBE Scientific Challenge organized during MEDICON 2019 where, in two phases, teams from all over the world tried to achieve the best possible object-detection accuracy based on the P300 signals. This paper presents the characteristics of the dataset and the approaches followed by the 9 finalist teams during the competition. The winner obtained an average accuracy of 92.3% with a convolutional neural network based on EEGNet. The dataset is now publicly released and stands as a benchmark for future P300-based BCI algorithms based on multiple session data.
Purpose To examine the mortality risk associated with diabetes in the Mexico City Diabetes Study (MCDS) and the San Antonio Heart Study (SAHS). Methods Prospective cohorts conducted 1990–2007 in MCDS ...and 1979–2000 in SAHS. Mortality risk was examined using Cox proportional hazard models in 1402 non-Hispanic whites (NHW), 1907 U.S.-born Mexican-Americans (MA), 444 Mexican-born MA, and 2281 Mexico City residents (MCR) between the ages of 35–64. Results Age- and sex-adjusted mortality hazard ratios (HR) comparing U.S.-born MA, Mexican-born MA, and MCR to NHW were 1.09 (95% confidence interval CI: 0.86, 1.37), 1.23 (95% CI: 0.86, 1.76), and 0.97 (95% CI: 0.77, 1.23), respectively, in nondiabetic individuals; in contrast, mortality risk varied in diabetic individuals with respective HRs of 1.77 (95% CI: 1.20, 2.61), 1.08 (95% CI: 0.59, 1.97), and 2.27 (95% CI: 1.53, 3.35) (interaction p = .0003). Excluding Mexican-born MA and nondiabetic individuals, controlling for medication use, insulin use, fasting glucose levels, and duration of diabetes explained a significant proportion of the mortality differential (HRs relative to NHW were 1.31 95% CI: 0.87, 1.98 in U.S.-born MA and 1.38 95% CI: 0.89, 2.12 in MCR). Conclusions This study provides evidence that diabetes is more lethal in U.S.-born MA and MCR than in NHW.
Microalbuminuria as a predictor of myocardial infarction in a Mexican population: The Mexico City Diabetes Study.
Our objective was to evaluate whether microalbuminuria predicts myocardial infarction ...(MI) in a Mexican population.
The study was a prospective, population-based cohort. Baseline examination was carried out in 1989; the first follow-up in 1993 and the second in 1997. All men and non-pregnant women between 35 and 64 years of age at the start of the study were considered eligible. Clinical, anthropometric, and laboratory characteristics were evaluated. All patients with macroalbuminuria at baseline were excluded from the present analyses, as were all prevalent cases with MI. Remaining patients were classified as with or without microalbuminuria. Incident cases of MI were identified during follow-up phases using an electrocardiogram (according to the Minnesota Code) or the death certificate (in which underlying cause of death was listed as MI, Causes of Death codes 410.0-410.9).
From 2196 individuals, 1586 satisfied the inclusion criteria. Two hundred fifteen (13.6%) had microalbuminuria, and 1371 (86.4%) did not. During follow-up, 10 patients with microalbuminuria and 31 patients without microalbuminuria developed an MI. Using robust logistic regression, the probability of developing MI, adjusting by Framingham score, was estimated to be 1.90 (95% CI,.97-3.72) times higher in patients with microalbuminuria as compared with patients without microalbuminuria.
We found that in a Mexican population the relationship between microalbuminuria and incidence of MI was borderline statistically significant after adjusting for other cardiovascular risk factors.
Significance Genome sequencing of individuals in the population reveals new mutations in almost every protein coding gene; interpreting the consequence of these mutations for human health and disease ...remains challenging. We sequenced the gene PPARG , a target of antidiabetic drugs, in nearly 20,000 individuals with and without type 2 diabetes (T2D). We identified 49 previously unidentified protein-altering mutations, characterized their cellular function in human cells, and discovered that nine of these mutations cause loss-of-function (LOF). The individuals who carry these nine LOF mutations have a sevenfold increased risk of T2D, whereas individuals carrying mutations we classify as benign have no increased risk of T2D.
Aims/hypothesis
The Latino population has been systematically underrepresented in large-scale genetic analyses, and previous studies have relied on the imputation of ungenotyped variants based on the ...1000 Genomes (1000G) imputation panel, which results in suboptimal capture of low-frequency or Latino-enriched variants. The National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) released the largest multi-ancestry genotype reference panel representing a unique opportunity to analyse rare genetic variations in the Latino population. We hypothesise that a more comprehensive analysis of low/rare variation using the TOPMed panel would improve our knowledge of the genetics of type 2 diabetes in the Latino population.
Methods
We evaluated the TOPMed imputation performance using genotyping array and whole-exome sequence data in six Latino cohorts. To evaluate the ability of TOPMed imputation to increase the number of identified loci, we performed a Latino type 2 diabetes genome-wide association study (GWAS) meta-analysis in 8150 individuals with type 2 diabetes and 10,735 control individuals and replicated the results in six additional cohorts including whole-genome sequence data from the All of Us cohort.
Results
Compared with imputation with 1000G, the TOPMed panel improved the identification of rare and low-frequency variants. We identified 26 genome-wide significant signals including a novel variant (minor allele frequency 1.7%; OR 1.37,
p
=3.4 × 10
−9
). A Latino-tailored polygenic score constructed from our data and GWAS data from East Asian and European populations improved the prediction accuracy in a Latino target dataset, explaining up to 7.6% of the type 2 diabetes risk variance.
Conclusions/interpretation
Our results demonstrate the utility of TOPMed imputation for identifying low-frequency variants in understudied populations, leading to the discovery of novel disease associations and the improvement of polygenic scores.
Data availability
Full summary statistics are available through the Common Metabolic Diseases Knowledge Portal (
https://t2d.hugeamp.org/downloads.html
) and through the GWAS catalog (
https://www.ebi.ac.uk/gwas/
, accession ID: GCST90255648). Polygenic score (PS) weights for each ancestry are available via the PGS catalog (
https://www.pgscatalog.org
, publication ID: PGP000445, scores IDs: PGS003443, PGS003444 and PGS003445).
Graphical abstract
Describing the prevalence and trends of cardiometabolic risk factors that are associated with non-communicable diseases (NCDs) is crucial for monitoring progress, planning prevention, and providing ...evidence to support policy efforts. We aimed to analyse the transition in body-mass index (BMI), obesity, blood pressure, raised blood pressure, and diabetes in the Americas, between 1980 and 2014.
We did a pooled analysis of population-based studies with data on anthropometric measurements, biomarkers for diabetes, and blood pressure from adults aged 18 years or older. A Bayesian model was used to estimate trends in BMI, raised blood pressure (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg), and diabetes (fasting plasma glucose ≥7·0 mmol/L, history of diabetes, or diabetes treatment) from 1980 to 2014, in 37 countries and six subregions of the Americas.
389 population-based surveys from the Americas were available. Comparing prevalence estimates from 2014 with those of 1980, in the non-English speaking Caribbean subregion, the prevalence of obesity increased from 3·9% (95% CI 2·2–6·3) in 1980, to 18·6% (14·3–23·3) in 2014, in men; and from 12·2% (8·2–17·0) in 1980, to 30·5% (25·7–35·5) in 2014, in women. The English-speaking Caribbean subregion had the largest increase in the prevalence of diabetes, from 5·2% (2·1–10·4) in men and 6·4% (2·6–10·4) in women in 1980, to 11·1% (6·4–17·3) in men and 13·6% (8·2–21·0) in women in 2014). Conversely, the prevalence of raised blood pressure has decreased in all subregions; the largest decrease was found in North America from 27·6% (22·3–33·2) in men and 19·9% (15·8–24·4) in women in 1980, to 15·5% (11·1–20·9) in men and 10·7% (7·7–14·5) in women in 2014.
Despite the generally high prevalence of cardiometabolic risk factors across the Americas, estimates also showed a high level of heterogeneity in the transition between countries. The increasing prevalence of obesity and diabetes observed over time requires appropriate measures to deal with these public health challenges. Our results support a diversification of health interventions across subregions and countries.
Wellcome Trust.
Estimates of the burden of cardio-metabolic risk factors in Latin America and the Caribbean (LAC) rely on relative risks (RRs) from non-LAC countries. Whether these RRs apply to LAC remains unknown.
...We pooled LAC cohorts. We estimated RRs per unit of exposure to body mass index (BMI), systolic blood pressure (SBP), fasting plasma glucose (FPG), total cholesterol (TC) and non-HDL cholesterol on fatal (31 cohorts, n=168,287) and non-fatal (13 cohorts, n=27,554) cardiovascular diseases, adjusting for regression dilution bias. We used these RRs and national data on mean risk factor levels to estimate the number of cardiovascular deaths attributable to non-optimal levels of each risk factor.
Our RRs for SBP, FPG and TC were like those observed in cohorts conducted in high-income countries; however, for BMI, our RRs were consistently smaller in people below 75 years of age. Across risk factors, we observed smaller RRs among older ages. Non-optimal SBP was responsible for the largest number of attributable cardiovascular deaths ranging from 38 per 100,000 women and 54 men in Peru, to 261 (Dominica, women) and 282 (Guyana, men). For non-HDL cholesterol, the lowest attributable rate was for women in Peru (21) and men in Guatemala (25), and the largest in men (158) and women (142) from Guyana.
RRs for BMI from studies conducted in high-income countries may overestimate disease burden metrics in LAC; conversely, RRs for SBP, FPG and TC from LAC cohorts are similar to those estimated from cohorts in high-income countries.
Wellcome Trust (214185/Z/18/Z)
Moderate-to-severe diabetic retinopathy is more prevalent in Mexico City than in San Antonio, Texas.
M E González Villalpando ,
C González Villalpando ,
B Arredondo Pérez ,
S V Martínez Díaz ,
B ...Mitchell ,
D Rivera Martínez ,
R Klein ,
S M Haffner and
M P Stern
Centro de Estudios en Diabetes, México. cgonzala@buzon.main.conacyt.mx
Abstract
OBJECTIVE: To compare the prevalence of diabetic retinopathy (DR) between low-income Mexicans from Mexico City and Mexican-Americans
from San Antonio, Texas. RESEARCH DESIGN AND METHODS: We designed a cross-sectional population-based study in low-income neighborhoods
of Mexico City and San Antonio. The men and non-pregnant women included in the study had NIDDM and were between 35 and 64
years of age. Ophthalmologic evaluation was performed in 414 patients, 204 in San Antonio and 210 in Mexico City. Seven field
standard stereophotographs of each eye were obtained, adapting the Early Treatment Diabetic Retinopathy Study protocol, and
graded at the Fundus Photograph Reading Center of the University of Wisconsin. RESULTS: Early nonproliferative DR occurred
in 37 (17.6%) and 39 (19.1%) patients in Mexico City and San Antonio, respectively. Moderate-to-severe nonproliferative DR
occurred in 55 (26.2%) and 37 (18.1%) patients in Mexico City and San Antonio, respectively, and proliferative DR occurred
in 12 (5.7%) and 7 (3.4%) patients in Mexico City and San Antonio, respectively. Using univariate and multivariate logistic
regression analysis with DR as the dependent variable, age, duration of disease, and fasting glucose concentration were positively
and significantly associated with retinopathy, whereas city, systolic blood pressure, and other selected metabolic variables
were not. We defined moderate-to-severe DR to include the categories of moderate-to-severe nonproliferative and proliferative
DR. For this combined category, Mexico City patients with diabetes had a significantly higher prevalence (P < 0.01) than those
from San Antonio when analyzed by multiple logistic regression analysis (odds ratio for Mexico City/San Antonio, 1.72; 95%
CI 1.10-2.70). CONCLUSIONS: Overall prevalence of DR is similar in both cities. However, moderate-to-severe DR is significantly
higher in Mexico City.
Background. There are no prospective data regarding the natural history of obesity in Mexico. The objective of this research was to investigate the incidence and progression of obesity in a ...low-income sector of Mexico City and to characterize evolution of body fat pattern distribution.
Methods. We carried out a population-based, prospective survey. Total on-site population was 15,532 persons; we determined as eligible all 35 to 64-year-old men and nonpregnant women for a total of 3,505. We interviewed at baseline 3,319 (94.7%) individuals and examined 2,282 (65.1%). At follow-up approximately 7 years later, we interviewed 1,764 (77.3%) subjects and examined 1,594 (69.9%). Measurements for all participants included height, weight, body mass index (BMI), waist-hip circumference, and subscapular and triceps skinfold thickness. Overweight was defined as BMI ≥25 and ≤29.9 kg/m
2, while grade 1 obesity was BMI ≥30 and ≤34.9 kg/m
2, grade 2 was ≥35 and ≤39.9, and grade 3, ≥40 kg/m
2.
Results. At baseline, prevalence of overweight was 48.6%, and grade 1 obesity, 22.7%, grade 2, 5.1%, and grade 3 obesity was 1.4%; at follow-up, these were 45.2, 25.8, 6.6, and 2.3%, respectively. At baseline, mean BMI in women was 29.1±0.16 kg/m
2 and in men, 27.3±0.15 kg/m
2; at follow-up, it reached 29.4±0.17 kg/m
2 in women and 27.4±0.16 kg/m
2 in men. Waist circumference increased from mean of 99.7±0.44 cm in women to 101.2±0.42 cm; in men, mean waist circumference rose from 95.2±0.38 to 96.7±0.39 cm.
Conclusions. The obesity epidemic in this population possesses serious proportions that increase risk for severe metabolic consequences. There is a need for intervention.
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