scholarly journals Mendelian randomization study of maternal influences on birthweight and future cardiometabolic risk in the HUNT cohort

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Gunn-Helen Moen ◽  
Ben Brumpton ◽  
Cristen Willer ◽  
Bjørn Olav Åsvold ◽  
Kåre I. Birkeland ◽  
...  

Abstract There is a robust observational relationship between lower birthweight and higher risk of cardiometabolic disease in later life. The Developmental Origins of Health and Disease (DOHaD) hypothesis posits that adverse environmental factors in utero increase future risk of cardiometabolic disease. Here, we explore if a genetic risk score (GRS) of maternal SNPs associated with offspring birthweight is also associated with offspring cardiometabolic risk factors, after controlling for offspring GRS, in up to 26,057 mother–offspring pairs (and 19,792 father–offspring pairs) from the Nord-Trøndelag Health (HUNT) Study. We find little evidence for a maternal (or paternal) genetic effect of birthweight associated variants on offspring cardiometabolic risk factors after adjusting for offspring GRS. In contrast, offspring GRS is strongly related to many cardiometabolic risk factors, even after conditioning on maternal GRS. Our results suggest that the maternal intrauterine environment, as proxied by maternal SNPs that influence offspring birthweight, is unlikely to be a major determinant of adverse cardiometabolic outcomes in population based samples of individuals.

Author(s):  
Gunn-Helen Moen ◽  
Ben Brumpton ◽  
Cristen Willer ◽  
Bjørn Olav Åsvold ◽  
Kåre Birkeland ◽  
...  

AbstractIntroductionThere is a robust and well-documented observational relationship between lower birthweight and higher risk of cardiometabolic disease in later life. The Developmental Origins of Health and Disease (DOHaD) hypothesis posits that adverse environmental factors in utero or in the early years of life result in increased future risk of cardiometabolic disease. Our aim was to investigate whether there was evidence for causal effects of the intrauterine environment, as proxied by maternal single nucleotide polymorphisms (SNPs) that influence offspring birthweight independent of offspring genotype, on offspring cardiometabolic risk factors such as blood pressure, non-fasting glucose, body mass index (BMI), and lipid levels.MethodsWe investigated whether a genetic risk score of maternal SNPs associated with offspring birthweight was also associated with offspring cardiometabolic risk factors, after controlling for offspring genotypes at the same loci, in up to 26,057 mother-offspring pairs from the Nord-Trøndelag Health (HUNT) Study. We also conducted similar analyses in 19,792 father-offspring pairs from the same study to investigate whether there was evidence that any such causal effects operated through the postnatal, rather than the intrauterine environment. To take account of the considerable cryptic relatedness in HUNT, we implemented a computationally efficient genetic linear mixed model using the OpenMx software package to perform our analyses.ResultsWe found little evidence for a maternal genetic effect of birthweight associated variants on offspring cardiometabolic risk factors after adjusting for offspring genotypes at the same loci. Likewise, we found little evidence for paternal genetic effects on offspring cardiometabolic risk factors performing similar analyses in father-offspring pairs. In contrast, offspring genetic risk scores of birthweight associated variants were strongly related to many cardiometabolic risk factors, even after conditioning on maternal genotypes at the same loci.ConclusionOur results suggest that the maternal intrauterine environment, as proxied by maternal SNPs that influence offspring birthweight, is unlikely to be a major determinant of adverse cardiometabolic outcomes in population based samples of individuals. In contrast, genetic pleiotropy appears to explain some of the observational relationship between offspring birthweight and future cardiometabolic risk.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Widet Gallo ◽  
Filip Ottosson ◽  
Cecilia Kennbäck ◽  
Amra Jujic ◽  
Jonathan Lou S. Esguerra ◽  
...  

Abstract Background Alterations in levels of circulating micro-RNAs might reflect within organ signaling or subclinical tissue injury that is linked to risk of diabetes and cardiovascular risk. We previously found that serum levels of miR-483-5p is correlated with cardiometabolic risk factors and incidence of cardiometabolic disease in a case–control sample from the populations-based Malmö Diet and Cancer Study Cardiovascular Cohort (MDC-CC). We here aimed at replicating these findings and to test for association with carotid atherosclerosis. Methods We measured miR-483-5p in fasting serum of 1223 healthy subjects from the baseline examination of the population-based, prospective cohort study Malmö Offspring Study (MOS) and correlated miR-483-5p to cardiometabolic risk factors and to incidence of diabetes mellitus and coronary artery disease (CAD) during 3.7 (± 1.3) years of follow-up using logistic regression. In both MOS and MDC-CC we related mir-483-5p to carotid atherosclerosis measured with ultrasound. Results In cross-sectional analysis miR-483-5p was correlated with BMI, waist circumference, HDL, and sex. After adjustment for age and sex, the association remained significant for all risk factors except for HDL. Logistic regression analysis showed significant associations between miR-483-5p and new-onset diabetes (OR = 1.94, 95% CI 1.06–3.56, p = 0.032) and cardiovascular disease (OR = 1.99, 95% CI 1.06–3.75, p = 0.033) during 3.7 (± 1.3) years of follow-up. Furthermore, miR-483-5p was significantly related with maximum intima-media thickness of the carotid bulb in MDC-CC (p = 0.001), but not in MOS, whereas it was associated with increasing number of plaques in MOS (p = 0.007). Conclusion miR-483-5p is related to an unfavorable cardiometabolic risk factor profile and predicts diabetes and CAD, possibly through an effect on atherosclerosis. Our results encourage further studies of possible underlying mechanisms and means of modifying miR-483-5p as a possible interventional target in prevention of cardiometabolic disease.


2021 ◽  
Vol 9 (2) ◽  
pp. 167-174
Author(s):  
Motahar Heidari-Beni ◽  
◽  
Roya Riahi ◽  
Fatemeh Mohebpour ◽  
Majid Khademian ◽  
...  

Context: There has been an increasing interest in epidemiological and clinical studies concerning the role of uric acid in cardiometabolic diseases, especially in children and adolescents. However, these potential relationships remain undiscovered; accordingly, its pathophysiological mechanisms remain unrecognized. This study aimed to assess the potential association between Serum Uric Acid (SUA) levels and cardiometabolic risk factors in a population-based sample of Iranian children and adolescents. Objectives: This study aimed to assess the potential association between Serum Uric Acid (SUA) levels and cardiometabolic risk factors in a population-based sample of Iranian children and adolescents. Methods: The data of 595 individuals aged 7-18 years were assessed in this research. Anthropometric measurements and laboratory tests were performed according to standardized protocols. Results: The Mean±SD age of the 595 explored students was 12.39±3.07 years. The overall Mean±SD SUA level of the study participants was measured as 4.22±1.13 mg/dL, with significant gender-wise differences (4.04±0.97 mg/dL vs 4.38±1.24 mg/dL, respectively; P<0.05). The prevalence of hyperuricemia based on the 90th percentile of SUA levels was equal to 10.6%. There was a positive association between SUA levels and abdominal obesity (waist circumference: ≥90th percentile) [Odds Ratio (OR): 1.54; 95% Confidence Interval (CI): 1.26 to 1.86] and general obesity [gender-specific Body Mass Index (BMI) for >95th percentile] (OR: 2.32; 95% CI: 1.74 to 3.11). Conclusions: This study suggested BMI and waist circumference as cardiometabolic risk factors, i.e. significantly associated with SUA levels in children and adolescents.


PLoS ONE ◽  
2011 ◽  
Vol 6 (4) ◽  
pp. e18865 ◽  
Author(s):  
Idris Guessous ◽  
Olivier Bonny ◽  
Fred Paccaud ◽  
Vincent Mooser ◽  
Gérard Waeber ◽  
...  

BMJ Open ◽  
2013 ◽  
Vol 3 (5) ◽  
pp. e002910 ◽  
Author(s):  
Jelena Djordjevic ◽  
Debbie A Lawlor ◽  
Alexei I Zhurov ◽  
Arshed M Toma ◽  
Rebecca Playle ◽  
...  

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
L. Madden Brewster ◽  
Tyler D Bammert ◽  
Jamie G Hijmans ◽  
Caitlin A Dow ◽  
Anabel Goulding ◽  
...  

Background: Obesity reduces the number of years lived free of cardiovascular disease (CVD) and increases the number of years lived with CVD, contributing to increased morbidity and mortality risk across all ages. Experimental and clinical studies indicate that a proatherogenic endothelial phenotype is a major consequence of increased adiposity and a primary mechanism underlying obesity-related CVD. Extracellular microvesicles, particularly endothelial cell-derived microvesicles (EMVs), are seminal functional modulators of vascular health and disease. The purpose of this study was to determine: 1) if circulating EMV levels are elevated with obesity, independent of other cardiometabolic risk factors; and if so, 2) whether circulating EMVs are associated with obesity-related endothelial vasodilator dysfunction. Methods: Thirty sedentary, middle-aged adults (45-63 years) were studied: 15 normal weight (10M/5F; age: 56±1 yr; BMI: 23.2±0.4 kg/m2; body fat: 25.1±2.4 %) and 15 obese (10M/5F; age: 54±1 yr; BMI: 31.5±0.3 kg/m2; body fat: 37.2±1.7 %). All subjects were free of other cardiometabolic risk factors and overt disease. EMV identification (CD31 + /42b - ) and concentration in peripheral blood were determined by flow cytometry. Forearm blood flow (FBF: via plethysmography) was assessed in response to intra-arterial infusions of acetylcholine (4.0, 8.0 and 16.0 μg/100 mL tissue/min) and sodium nitroprusside (1.0, 2.0 and 4.0 μg/100 mL tissue/min). Results: Circulating EMV levels were ~100% higher (P<0.05) in obese (182±14 EMV/μL) compared with normal weight (91±12 EMV/μL) adults. FBF response to acetylcholine was significantly lower (~35%) in the obese (from 4.0±0.2 to 10.3±0.6 mL/100 mL tissue/min vs 4.3±0.3 to 15.4±0.8 mL/100 mL tissue/min) group. Circulating EMVs were significantly and inversely associated with total FBF response to acetylcholine (r=-0.55). Conclusions: Obesity, independent of other cardiometabolic risk factors, is associated with elevated circulating levels of EMVs. Higher circulating EMVs in obese adults may contribute to adiposity-related endothelial dysfunction and vascular disease risk. Indeed, circulating EMVs have been linked to disease risk, severity and outcome in other high-risk populations.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Brian Houle ◽  
Thomas Gaziano ◽  
Meagan Farrell ◽  
F. Xavier Gómez-Olivé ◽  
Lindsay C. Kobayashi ◽  
...  

Abstract Background Evidence on cognitive function in older South Africans is limited, with few population-based studies. We aimed to estimate baseline associations between cognitive function and cardiometabolic disease risk factors in rural South Africa. Methods We use baseline data from “Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa” (HAALSI), a population-based study of adults aged 40 and above in rural South Africa in 2015. Cognitive function was measured using measures of time orientation, immediate and delayed recall, and numeracy adapted from the Health and Retirement Study cognitive battery (overall total cognitive score range 0–26). We used multiple linear regression to estimate associations between cardiometabolic risk factors (including BMI, hypertension, dyslipidemia, diabetes, history of stroke, alcohol frequency, and smoking status) and the overall cognitive function score, adjusted for potential confounders. Results In multivariable-adjusted analyses (n = 3018; male = 1520; female = 1498; median age 59 (interquartile range 50–67)), cardiometabolic risk factors associated with lower cognitive function scores included: diabetes (b = − 1.11 [95% confidence interval: − 2.01, − 0.20] for controlled diabetes vs. no diabetes); underweight BMI (b = − 0.87 [CI: − 1.48, − 0.26] vs. normal BMI); and current and past smoking history compared to never smokers. Factors associated with higher cognitive function scores included: obese BMI (b = 0.74 [CI: 0.39, 1.10] vs. normal BMI); and controlled hypertension (b = 0.53 [CI: 0.11, 0.96] vs. normotensive). Conclusions We provide an important baseline from rural South Africa on the associations between cardiometabolic disease risk factors and cognitive function in an older, rural South African population using standardized clinical measurements and cut-offs and widely used cognitive assessments. Future studies are needed to clarify temporal associations as well as patterns between the onset and duration of cardiometabolic conditions and cognitive function. As the South African population ages, effective management of cardiometabolic risk factors may be key to lasting cognitive health.


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