Prevalent Cocaine Use and Myocardial Infarction Aslibekyan, Stella, SM; Levitan, Emily B., ScD; Mittleman, Murray A., MD, DrPH
The American journal of cardiology,
10/2008, Volume:
102, Issue:
8
Journal Article
Peer reviewed
Open access
Studies have reported a possible link between cocaine use and risk for cardiovascular events. The aim of this study was to examine the association between self-reported cocaine use and ...physician-diagnosed myocardial infarction (MI) in the Third National Health and Nutrition Examination Survey (NHANES III), conducted from 1988 to 1994. Odds ratios (ORs) were estimated using logistic regression models adjusted for age and additionally for gender, race, and other MI risk factors, which accounted for the complex sampling design. In the group aged 18 to 59 years, there was no statistically significant association between any exposure to cocaine and MI (age-adjusted OR 1.56, 95% confidence interval CI 0.44 to 5.50, p = 0.48; multivariate-adjusted OR 1.06, 95% CI 0.30 to 3.73, p = 0.92). Participants who reported using cocaine >10 times had a nonsignificant higher prevalence of MI (age-adjusted OR 3.13, 95% CI 0.80 to 12.25, p = 0.10; multivariate-adjusted OR 1.84, 95% CI 0.46 to 7.29, p = 0.40). However, participants aged 18 to 45 years who reported >10 occasions of cocaine use had a significantly elevated prevalence of MI in age-adjusted models (OR 4.60, 95% CI 1.12 to 18.88, p = 0.035). The association was attenuated in multivariate-adjusted models (OR 3.84, 95% CI 0.98 to 15.07, p = 0.054). The lifetime prevalence of cocaine use increased from 14% in NHANES III to 19% in NHANES 2005–2006. In conclusion, these data support a substantial association between cocaine use and MI; the temporal trend in cocaine use may increase the occurrence of MI, particularly in younger populations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
GAW20 provided a platform for developing and evaluating statistical methods to analyze human lipid-related phenotypes, DNA methylation, and single-nucleotide markers in a study involving a ...pharmaceutical intervention. In this article, we present an overview of the data sets and the contributions analyzing these data. The data, donated by the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) investigators, included data from 188 families (
= 1105) which included genome-wide DNA methylation data before and after a 3-week treatment with fenofibrate, single-nucleotide polymorphisms, metabolic syndrome components before and after treatment, and a variety of covariates. The contributions from individual research groups were extensively discussed prior, during, and after the Workshop in groups based on discussion themes, before being submitted for publication.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The objective of this study is to provide an assessment of allostatic load (AL) burden among US adults across race/ethnicity, gender, and age groups over a 30-year time period. We analyzed data from ...50,671 participants of the National Health and Nutrition Examination Survey (NHANES) years 1988 through 2018. AL score was defined as the sum total for abnormal measures of the following components: serum albumin, body mass index, serum C – reactive protein, serum creatinine, diastolic blood pressure, glycated hemoglobin, systolic blood pressure, total cholesterol, and serum triglycerides. We performed modified Poisson regression to estimate the adjusted Relative Risks (aRRs) of allostatic load, and generalized linear models to determine adjusted mean differences accounting for NHANES sampling weights. Among US adults aged 18 or older, the prevalence of high AL increased by more than 45% from 1988 to 1991 to 2015–2018, from 33.5% to 48.6%. By the latest period, 2015–2018, Non-Hispanic Black women (aRR: 1.292; 95% CI: 1.290–1.293) and Latina women (aRR: 1.266; 95% CI: 1.265–1.267) had higher risks of AL than non-Hispanic White women. Similar trends were observed among men. Age-adjusted mean AL score among NH-Black and Latinx adults was higher than for NH-Whites of up to a decade older regardless of gender. From 1988 through 2018, Adults aged 40 years old and older had over 2-fold increased risks of high AL when compared to adults 18–29 years old. After 30-years of collective data, racial disparities in allostatic load persist for NH-Black and Latinx adults.
•Allostatic load (AL) is a measure of biologic wear and tear due to chronic stress.•We estimated AL over a 30-year period using US national survey data.•Overall, mean AL scores increased by 45.1% from 1988 to 1991 to 2015–2018.•Regardless of time period, Black and Latinos had increased risk of high AL.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving ...diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes)
. In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Age is the dominant risk factor for most chronic human diseases, but the mechanisms through which ageing confers this risk are largely unknown
. The age-related acquisition of somatic mutations that ...lead to clonal expansion in regenerating haematopoietic stem cell populations has recently been associated with both haematological cancer
and coronary heart disease
-this phenomenon is termed clonal haematopoiesis of indeterminate potential (CHIP)
. Simultaneous analyses of germline and somatic whole-genome sequences provide the opportunity to identify root causes of CHIP. Here we analyse high-coverage whole-genome sequences from 97,691 participants of diverse ancestries in the National Heart, Lung, and Blood Institute Trans-omics for Precision Medicine (TOPMed) programme, and identify 4,229 individuals with CHIP. We identify associations with blood cell, lipid and inflammatory traits that are specific to different CHIP driver genes. Association of a genome-wide set of germline genetic variants enabled the identification of three genetic loci associated with CHIP status, including one locus at TET2 that was specific to individuals of African ancestry. In silico-informed in vitro evaluation of the TET2 germline locus enabled the identification of a causal variant that disrupts a TET2 distal enhancer, resulting in increased self-renewal of haematopoietic stem cells. Overall, we observe that germline genetic variation shapes haematopoietic stem cell function, leading to CHIP through mechanisms that are specific to clonal haematopoiesis as well as shared mechanisms that lead to somatic mutations across tissues.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Late-onset Alzheimer's disease is a prevalent age-related polygenic disease that accounts for 50-70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer's ...disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer's disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer's disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer's disease to identify further genetic variants that contribute to Alzheimer's pathology.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Background
Left ventricular (LV) hypertrophy affects up to 43% of African Americans (AAs). Antihypertensive treatment reduces LV mass (LVM). However, interindividual variation in LV traits in ...response to antihypertensive treatments exists. We hypothesized that genetic variants may modify the association of antihypertensive treatment class with LV traits measured by echocardiography.
Methods
We evaluated the main effects of the three most common antihypertensive treatments for AAs as well as the single nucleotide polymorphism (SNP)‐by‐drug interaction on LVM and relative wall thickness (RWT) in 2,068 participants across five community‐based cohorts. Treatments included thiazide diuretics (TDs), angiotensin converting enzyme inhibitors (ACE‐Is), and dihydropyridine calcium channel blockers (dCCBs) and were compared in a pairwise manner. We performed fixed effects inverse variance weighted meta‐analyses of main effects of drugs and 2.5 million SNP‐by‐drug interaction estimates.
Results
We observed that dCCBs versus TDs were associated with higher LVM after adjusting for covariates (p = 0.001). We report three SNPs at a single locus on chromosome 20 that modified the association between RWT and treatment when comparing dCCBs to ACE‐Is with consistent effects across cohorts (smallest p = 4.7 × 10−8, minor allele frequency range 0.09–0.12). This locus has been linked to LV hypertrophy in a previous study. A marginally significant locus in BICD1 (rs326641) was validated in an external population.
Conclusions
Our study identified one locus having genome‐wide significant SNP‐by‐drug interaction effect on RWT among dCCB users in comparison to ACE‐I users. Upon additional validation in future studies, our findings can enhance the precision of medical approaches in hypertension treatment.
This study highlights the potential impact of antihypertensive treatments as well as their pharmacogenetic effect of on left ventricular (LV) traits in African Americans among 2,068 participants across five community‐based cohorts. Dihydropyridine calcium channel blocker (dCCB) use was observed to be associated with greater LV mass than thiazide diuretic use. A single locus on chromosome 20 was also identified to modify the association between relative wall thickness and treatment when comparing dCCBs to angiotensin converting enzyme inhibitors with consistent effects across cohorts.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
COVID-19 presents with a wide range of severity, from asymptomatic in some individuals to fatal in others. Based on a study of 1,051,032 23andMe research participants, we report genetic and ...nongenetic associations with testing positive for SARS-CoV-2, respiratory symptoms and hospitalization. Using trans-ancestry genome-wide association studies, we identified a strong association between blood type and COVID-19 diagnosis, as well as a gene-rich locus on chromosome 3p21.31 that is more strongly associated with outcome severity. Hospitalization risk factors include advancing age, male sex, obesity, lower socioeconomic status, non-European ancestry and preexisting cardiometabolic conditions. While non-European ancestry was a significant risk factor for hospitalization after adjusting for sociodemographics and preexisting health conditions, we did not find evidence that these two primary genetic associations explain risk differences between populations for severe COVID-19 outcomes.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
To characterise dietary habits, their temporal and spatial patterns and associations with BMI in the 23andMe study population.
We present a large-scale cross-sectional analysis of self-reported ...dietary intake data derived from the web-based National Health and Nutrition Examination Survey 2009-2010 dietary screener. Survey-weighted estimates for each food item were characterised by age, sex, race/ethnicity, education and BMI. Temporal patterns were plotted over a 2-year time period, and average consumption for select food items was mapped by state. Finally, dietary intake variables were tested for association with BMI.
US-based adults 20-85 years of age participating in the 23andMe research programme.
Participants were 23andMe customers who consented to participate in research (n 526 774) and completed web-based surveys on demographic and dietary habits.
Survey-weighted estimates show very few participants met federal recommendations for fruit: 2·6 %, vegetables: 5·9 % and dairy intake: 2·8 %. Between 2017 and 2019, fruit, vegetables and milk intake frequency declined, while total dairy remained stable and added sugars increased. Seasonal patterns in reporting were most pronounced for ice cream, chocolate, fruits and vegetables. Dietary habits varied across the USA, with higher intake of sugar and energy dense foods characterising areas with higher average BMI. In multivariate-adjusted models, BMI was directly associated with the intake of processed meat, red meat, dairy and inversely associated with consumption of fruit, vegetables and whole grains.
23andMe research participants have created an opportunity for rapid, large-scale, real-time nutritional data collection, informing demographic, seasonal and spatial patterns with broad geographical coverage across the USA.
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