Chronic periodontitis (CP) is a common oral disease that confers substantial systemic inflammatory and microbial burden and is a major cause of tooth loss. Here, we present the results of a ...genome-wide association study of CP that was carried out in a cohort of 4504 European Americans (EA) participating in the Atherosclerosis Risk in Communities (ARIC) Study (mean age-62 years, moderate CP-43% and severe CP-17%). We detected no genome-wide significant association signals for CP; however, we found suggestive evidence of association (P < 5 × 10(-6)) for six loci, including NIN, NPY, WNT5A for severe CP and NCR2, EMR1, 10p15 for moderate CP. Three of these loci had concordant effect size and direction in an independent sample of 656 adult EA participants of the Health, Aging, and Body Composition (Health ABC) Study. Meta-analysis pooled estimates were severe CP (n = 958 versus health: n = 1909)-NPY, rs2521634 G: odds ratio OR = 1.49 (95% confidence interval (CI = 1.28-1.73, P = 3.5 × 10(-7))); moderate CP (n = 2293)-NCR2, rs7762544 G: OR = 1.40 (95% CI = 1.24-1.59, P = 7.5 × 10(-8)), EMR1, rs3826782 A: OR = 2.01 (95% CI = 1.52-2.65, P = 8.2 × 10(-7)). Canonical pathway analysis indicated significant enrichment of nervous system signaling, cellular immune response and cytokine signaling pathways. A significant interaction of NUAK1 (rs11112872, interaction P = 2.9 × 10(-9)) with smoking in ARIC was not replicated in Health ABC, although estimates of heritable variance in severe CP explained by all single nucleotide polymorphisms increased from 18 to 52% with the inclusion of a genome-wide interaction term with smoking. These genome-wide association results provide information on multiple candidate regions and pathways for interrogation in future genetic studies of CP.
Pathological shifts of the human microbiome are characteristic of many diseases, including chronic periodontitis. To date, there is limited evidence on host genetic risk loci associated with ...periodontal pathogen colonization. We conducted a genome-wide association (GWA) study among 1,020 white participants of the Atherosclerosis Risk in Communities Study, whose periodontal diagnosis ranged from healthy to severe chronic periodontitis, and for whom “checkerboard” DNA-DNA hybridization quantification of 8 periodontal pathogens was performed. We examined 3 traits: “high red” and “high orange” bacterial complexes, and “high” Aggregatibacter actinomycetemcomitans (Aa) colonization. Genotyping was performed on the Affymetrix 6.0 platform. Imputation to 2.5 million markers was based on HapMap II-CEU, and a multiple-test correction was applied (genome-wide threshold of p < 5 × 10−8). We detected no genome-wide significant signals. However, 13 loci, including KCNK1, FBXO38, UHRF2, IL33, RUNX2, TRPS1, CAMTA1, and VAMP3, provided suggestive evidence (p < 5 × 10−6) of association. All associations reported for “red” and “orange” complex microbiota, but not for Aa, had the same effect direction in a second sample of 123 African-American participants. None of these polymorphisms was associated with periodontitis diagnosis. Investigations replicating these findings may lead to an improved understanding of the complex nature of host-microbiome interactions that characterizes states of health and disease.
Objectives: To examine the longitudinal relationship between occupational and domestic sources of physical activity and body weight in a sample of Chinese adults. Methods: Population-based ...longitudinal observational study of Chinese adults (4697 women and 4708 men) aged 18-55 from the 1991, 1993, 1997, and 2000 waves of the China Health and Nutrition Survey. Measured height and weight and detailed self-reported energy expenditure from multiple occupational and domestic sources were assessed over a 9-year period. Longitudinal relationships were modeled using linear random effects models. Results: Increased occupational physical activity resulted in overall lower body weight for both men and women (β-coefficients (95% confidence interval (CI)) for high levels: -0.46 (-0.76, -0.15) for men, -0.36 (-0.62, -0.10) for women, and increased domestic physical activity resulted in overall lower body weight in men (β-coefficient (95% CI): -0.40 (-0.62, -0.18)). Conclusions: Physical activity that occurs in the occupational and domestic sectors is often overlooked; yet our research suggests they have important effects on body weight in Chinese adults. As China continues to urbanize, energy expenditure from these sources is decreasing, and our results point out the need to explore these types of physical activity more broadly across the world as potential sources of weight gain.
China has recently undergone rapid social and economic change. Increases in urbanization have led to equally rapid shifts toward more sedentary occupations through the acquisition of new technology ...and transitions away from a mostly agricultural economy. Our purpose was to utilize a detailed measure of urbanicity comprising 10 dimensions of urban services and infrastructure to examine its effects on the occupational physical activity patterns of Chinese adults. Longitudinal data were from individuals aged 18–55 from the years 1991–1997 of the China Health and Nutrition Survey (
N=4376 men and 4384 women). Logistic multilevel regression analyses indicated that men had 68% greater odds, and women had 51% greater odds, of light versus heavy occupational activity given the mean change in urbanization over the 6-year period. Further, simulations showed that light occupational activity increased linearly with increasing urbanization. After controlling for individual-level predictors, community-level urbanization explained 54% and 40% of the variance in occupational activity for men and women, respectively. This study provides empirical evidence of the reduction in intensity of occupational activity with modernization. It is likely that urbanization will continue unabated in China and this is liable to lead to further transitions in the labor market resulting in additional reductions in work-related activity. Because occupational activity remains the major source of energy expenditure for adults, unless alternative forms are widely adopted, the Chinese population is at risk of dramatic increases in the numbers of overweight and obese individuals.
To determine whether 4 genetic variants in the fat mass and obesity associated gene (FTO) identified in genome-wide association studies of diabetes and obesity are associated with cognitive change in ...midlife in the Atherosclerosis Risk in Communities (ARIC) Study.
ARIC is a prospective cohort study of the development of atherosclerosis in 15,792 individuals aged 45 to 64 years at baseline from 1986 to 1989. FTO is highly expressed in human fetal and adult brain, and a single nucleotide polymorphism in FTO has previously been associated with reduced brain volume in cognitively normal subjects. Since a relationship between brain atrophy and diminished cognitive function has been demonstrated in ARIC participants, general linear models were used to evaluate the association between 6-year change in scores on 3 neuropsychological tests and FTO genotype.
In a sample of 8,364 white and 2,083 African American men and women with no clinical history of stroke, significantly greater mean change in performance on the Delayed Word Recall Test was associated with 2 of 4 FTO single nucleotide polymorphisms examined (rs9939609, rs805136, rs17817449, and rs1421085) in whites but not in African Americans (p ≤ 0.002). The association of the FTO polymorphisms with cognitive change was independent of potential confounding clinical and demographic variables including age, gender, education, diabetes, hypertension, and body mass index.
Further studies will be needed to clarify the biological mechanisms and genetic pathways through which variants in FTO can increase susceptibility to decline in verbal memory detectable in middle-aged, community-dwelling adults.
Recent studies have identified chromosomal regions linked to variation in high density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (apo A-1) and triglyceride (TG), although results have been ...inconsistent and previous studies of American Indian populations are limited.
In an attempt to localise quantitative trait loci (QTLs) influencing HDL-C, apo A-1 and TG, we conducted genome-wide linkage scans of subjects of the Strong Heart Family Study.
We implemented analyses in 3484 men and women aged 18 years or older, at three study centres.
With adjustment for age, sex and centre, we detected a QTL influencing both HDL-C (logarithm of odds (LOD) = 4.4, genome-wide p = 0.001) and apo A-1 (LOD = 3.2, genome-wide p = 0.020) nearest marker D6S289 at 6p23 in the Arizona sample. Another QTL influencing apo A-1 was found nearest marker D9S287 at 9q22.2 (LOD = 3.0, genome-wide p = 0.033) in the North and South Dakotas. We detected a QTL influencing TG nearest marker D15S153 at 15q22.31 (LOD = 4.5 in the overall sample and LOD = 3.8 in the Dakotas sample, genome-wide p = 0.0044) and when additionally adjusted for waist, current smoking, current alcohol, current oestrogen, lipid treatment, impaired fasting glucose, and diabetes, nearest marker D10S217 at 10q26.2 (LOD = 3.7, genome-wide p = 0.0058) in the Arizona population.
The replication of QTLs in regions of the genome that harbour well known candidate genes suggest that chromosomes 6p, 9q and 15q warrant further investigation with fine mapping for causative polymorphisms in American Indians.
Abstract
Background
Most prior research on outcomes among older adults with established cardiovascular diseases focuses on recurrent events and hospitalizations. However, older adults value financial ...security and functional independence in addition to these disease-focused metrics. Recurrent cardiovascular events may increase risk of long-term nursing home residence and financial strain.
Purpose
To compare the risk for death, debility (long-term residence in a nursing home), and destitution (eligibility for health insurance programs for impoverished individuals) among older adults with recurrent myocardial infarction (MI) and controls.
Methods
We conducted a retrospective cohort study using administrative data from the United States Medicare program, a health insurance program for older adults. Among all patients who experienced a first overnight hospitalization with a discharge diagnosis of MI between 1 January 2007 and 30 June 2016, we identified patients with a recurrent MI hospitalization. Additionally, we selected controls from the same population of patients with MI, matched on calendar year of the initial MI and days since the initial MI. We included 194,481 patients aged 66 years and older with recurrent MI hospitalizations and 777,924 controls. Patients were followed for death, debility, and destitution until 31 December 2016. We used Kaplan-Meier curves and Cox proportional hazards models adjusted for sociodemographic factors, comorbidities, and healthcare utilization to compare patients with recurrent MI and matched controls.
Results
The average age of the population was 80.0 (standard deviation 8.3) years and 56.7% were women. Patients with recurrent MI were more likely to have a history of diabetes, chronic kidney disease, heart failure and peripheral artery disease than controls. The cumulative incidence of death, debility, and destitution were all higher among patients with recurrent MI than their matched controls (Figure). Comparing patients with recurrent MI to controls, the hazard ratios (95% confidence intervals) were 2.11 (2.09–2.13) for death, 0.92 (0.89–0.94) for debility, and 1.34 (1.29–1.39) for destitution after multivariable adjustment.
Death, debility, and destitution
Conclusion
Preventing recurrent MIs has the potential to reduce not only mortality but also destitution.
Acknowledgement/Funding
Amgen, Inc
Familial hypercholesterolemia (FH) is a condition characterized by high cholesterol levels and increased risk for coronary heart disease (CHD) that often goes undiagnosed. The Dutch Lipid Network ...Criteria (DLNC) are used to identify FH in clinical settings via physical examination, personal and family history of CHD, in addition to the presence of deleterious mutations of the
,
, and
genes. Agreement between clinical and genetic diagnosis of FH varies. While an ICD diagnosis code was not available for coding FH until 2016, Systematized Nomenclature of Medicine (SNOMED) clinical concept codes, including genetic diagnoses, for FH have been utilized in electronic health records (EHRs).
To evaluate the concordance of identifying FH via SNOMED and ICD-10 CM codes vs the DLNC in an EHR database.
Using the Practice Fusion EHR database, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated comparing an FH cohort identified via SNOMED and ICD-10 CM codes to one identified via the DLNC.
Among 907,616 patients with hypercholesterolemia, 2,180 were identified as FH via SNOMED code (zero were identified via ICD-10 CM), 259 had a DLNC score 6-8 (probable FH), and 45 had a DLNC score >8 (definite FH). Compared to DLNC score >8, the sensitivity, specificity, and PPV of the FH SNOMED code were 84.4%, 99.4%, and 6.4%, respectively. Compared to DLNC score ≥6, the sensitivity was 36.8% and the specificity was 99.5% with a PPV of 18.7%.
Compared to the clinical criteria for FH, identification of FH patients via SNOMED diagnosis codes had high sensitivity and specificity, but low PPV. The discordance of these two techniques in identifying FH patients speaks to the challenges in identifying FH patients in large electronic databases such as administrative claims and EHR.
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