scholarly journals Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

2018 ◽  
Author(s):  
Nicole M Warrington ◽  
Robin N Beaumont ◽  
Momoko Horikoshi ◽  
Felix R Day ◽  
Øyvind Helgeland ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Birth Weight ◽  
Indirect Effects ◽  
Structural Equation ◽  
Disease Risk ◽  
Genetic Effects ◽  
Intrauterine Environment ◽  
Fetal Genotype ◽  
Genotype Effects ◽  
Shared Genetic

AbstractBirth weight (BW) variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. These associations have been proposed to reflect the lifelong consequences of an adverse intrauterine environment. In earlier work, we demonstrated that much of the negative correlation between BW and adult cardio-metabolic traits could instead be attributable to shared genetic effects. However, that work and other previous studies did not systematically distinguish the direct effects of an individual’s own genotype on BW and subsequent disease risk from indirect effects of their mother’s correlated genotype, mediated by the intrauterine environment. Here, we describe expanded genome-wide association analyses of own BW (n=321,223) and offspring BW (n=230,069 mothers), which identified 278 independent association signals influencing BW (214 novel). We used structural equation modelling to decompose the contributions of direct fetal and indirect maternal genetic influences on BW, implicating fetal- and maternal-specific mechanisms. We used Mendelian randomization to explore the causal relationships between factors influencing BW through fetal or maternal routes, for example, glycemic traits and blood pressure. Direct fetal genotype effects dominate the shared genetic contribution to the association between lower BW and higher type 2 diabetes risk, whereas the relationship between lower BW and higher later blood pressure (BP) is driven by a combination of indirect maternal and direct fetal genetic effects: indirect effects of maternal BP-raising genotypes act to reduce offspring BW, but only direct fetal genotype effects (once inherited) increase the offspring’s later BP. Instrumental variable analysis using maternal BW-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring BP. In successfully separating fetal from maternal genetic effects, this work represents an important advance in genetic studies of perinatal outcomes, and shows that the association between lower BW and higher adult BP is attributable to genetic effects, and not to intrauterine programming.

scholarly journals Association between birth weight and childhood cardiovascular disease risk factors in West Virginia

2019 ◽  
Vol 11 (1) ◽  
pp. 86-95
Author(s):  
Amna Umer ◽  
Candice Hamilton ◽  
Lesley Cottrell ◽  
Peter Giacobbi ◽  
Kim Innes ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Birth Weight ◽  
West Virginia ◽  
Disease Risk ◽  
Density Lipoprotein ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
The Relationship

AbstractThe reported associations between birth weight and childhood cardiovascular disease (CVD) risk factors have been inconsistent. In this study, we investigated the relationship between birth weight and CVD risk factors at 11 years of age. This study used longitudinally linked data from three cross-sectional datasets (N = 22,136) in West Virginia; analysis was restricted to children born full-term (N = 19,583). The outcome variables included resting blood pressure [systolic blood pressure (SBP), diastolic blood pressure (DBP)] and lipid profile [total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL, and triglycerides (TG)]. Multiple regression analyses were performed, adjusting for child’s body mass index (BMI), sociodemographics, and lifestyle characteristics. Unadjusted analyses showed a statistically significant association between birth weight and SBP, DBP, HDL, and TG. When adjusted for the child’s BMI, the association between birth weight and HDL [b = 0.14 (95% CI: 0.11, 0.18) mg/dl per 1000 g increase] and between birth weight and TG [b = –0.007 (–0.008, –0.005) mg/dl per 1000 g increase] remained statistically significant. In the fully adjusted model, low birth weight was associated with higher LDL, non-HDL, and TGs, and lower HDL levels. The child’s current BMI at 11 years of age partially (for HDL, non-HDL, and TG) and fully mediated (for SBP and DBP) the relationship between birth weight and select CVD risk factors. While effects were modest, these risk factors may persist and amplify with age, leading to potentially unfavorable consequences in later adulthood.

Birth Weight Does Not Predict Blood Pressure in a Young Working Population: A Sharp (Scottish Heart and Arterial Disease Risk Prevention) Study

2008 ◽  
Vol 18 (4) ◽  
pp. 298-301 ◽  
Author(s):  
Gillian Libby ◽  
Shirley R. McEwan ◽  
Jill J. Belch ◽  
Andrew D. Morris
Keyword(s):  
Blood Pressure ◽  
Birth Weight ◽  
Disease Risk ◽  
Arterial Disease ◽  
Risk Prevention ◽  
Prevention Study ◽  
Working Population

scholarly journals Maternal investment, life-history trajectory of the off-spring and cardiovascular disease risk in Emirati females in the United Arab Emirates

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rola Al Ghali ◽  
Linda Smail ◽  
Maryam Muqbel ◽  
Dalia Haroun
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Life History ◽  
Birth Weight ◽  
Waist Circumference ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Maternal Investment ◽  
Age At Menarche ◽  
Menarcheal Age

Abstract Background Variations in cardiovascular disease risk (CVD) are suggested to be partly influenced by factors that affect prenatal growth patterns and outcomes, namely degree of maternal investment (proxied by birth weight and gestational age). Using the life history trajectory model, this study investigates whether maternal investment in early prenatal life associates with menarcheal age and whether maternal investment affects CVD risk in adulthood and predicts adult size and adiposity levels. Methods A cross-sectional study was conducted among 94 healthy Emirati females. Birth weight, gestational age and menarcheal age were obtained. Anthropometrical measurements, body composition analysis, and blood pressure values were collected. Regression analyses were conducted to establish associations. Results There was no association between birth weight standard deviation score (SDS) and age at menarche. When investigating the associations of birth weight SDS and age at menarche with growth indices, it was found that only birth weight was positively and significantly associated with both height (β = 1.342 cm, 95% CI (0.12, 2.57), p = 0.032) and leg length (β = 0.968 cm, 95% CI (0.08, 1.86), p = 0.034). Menarcheal age was significantly and inversely associated with fat mass index (FMI) (β = − 0.080 cm, 95% CI (− 0.13, − 0.03), p = 0.002), but not with waist circumference and fat free mass index (FFMI) (p > 0.05). Birth weight SDS was positively and significantly associated with waist circumference (β = 0.035 cm, 95% CI (0.01, 0.06), p = 0.009), FMI (β = 0.087 cm, 95% CI (0.01, 0.16), p = 0.027), and FFMI (β = 0.485 cm, 95% CI (0.17, 0.80), p = 0.003). Birth weight SDS was not significantly associated with either systolic blood pressure (SBP) or diastolic blood pressure (DBP) (p > 0.05). However, FMI, waist circumference, and FFMI were positively and significantly associated with SBP. Regarding DBP, the relationship was negatively and significantly associated with only FFMI (β = − 1.6111 kg/m2, 95% CI (− 2.63, − 0.60), p = 0.002). Conclusion Although the results do not fully support that Emirati females fast-life history is associated with increased chronic disease risk, the data does suggest a link between restricted fetal growth in response to low maternal investment and metabolic and reproductive health.

Nephron numbers and hyperfiltration as drivers of progression

2015 ◽  
Author(s):  
Valerie A. Luyckx
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Birth Weight ◽  
Renal Disease ◽  
Disease Risk ◽  
Kidney Diseases ◽  
Perinatal Care ◽  
Later Life ◽  
Nephron Number ◽  
Increased Risk

The relationship between low birth weight (LBW) and subsequent increased risk of hypertension and renal disease in humans is now well established. The initial hypothesis suggested that an adverse intrauterine environment, reflected by LBW, would impact renal development, resulting in a low nephron number and predisposition to hypertension and renal disease. Studies in various populations have shown a direct correlation between birth weight and nephron number, and in infants, nephron numbers are reduced in those of LBW. Among Caucasian and Australian Aboriginal adults, lower nephron numbers are associated with higher blood pressure, whereas higher nephron numbers appear to protect against hypertension. LBW is currently the best clinical surrogate for low nephron number and has been independently associated with higher blood pressure from infancy through to adulthood in many populations, as well as an increased risk of proteinuria, reduced glomerular filtration rate, chronic kidney disease, and end-stage renal disease in later life. The pathophysiology is analogous to that in other chronic kidney diseases where surviving nephrons are subject to hyperfiltration early on, resulting in glomerular hypertrophy, proteinuria, and eventually, especially in the setting of other renal disease risk factors, glomerulosclerosis, and loss of renal function. Mean nephron number varies by up to 13-fold in certain populations, however, therefore nephron number is unlikely the sole developmentally programmed risk factor for renal disease in later life, but may be a first ‘hit’ impacting an individual’s susceptibility to or resistance to superimposed renal injury. Augmentation of nephron number perinatally has only been addressed in experimental settings. In humans, therefore optimization of nephron number is likely best achieved through good perinatal care and adequate postnatal nutrition. Cardiovascular disease and diabetes are also developmentally programmed and therefore likely coexist in subjects with LBW and low nephron numbers. Awareness of an individual’s birth weight should serve to highlight the possibility of low nephron number and potential risk for future hypertension and renal disease, which may be attenuated by optimization of early nutrition, lifestyle choices, and management of other risk factors for renal disease.

scholarly journals The Genetic Architecture of Alzheimer’s Disease Risk: A Genomic Structural Equation Modelling Study

2021 ◽  
Author(s):  
Isabelle F Foote ◽  
Benjamin M Jacobs ◽  
Georgina Mathlin ◽  
Cameron J Watson ◽  
Phazha LK Bothongo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Structural Equation Modelling ◽  
Structural Equation ◽  
Genetic Architecture ◽  
Disease Risk ◽  
Modifiable Risk Factors ◽  
Equation Modelling ◽  
Shared Genetic

AbstractBackgroundTargeting modifiable risk factors may have a role in the prevention of Alzheimer’s disease. However, the mechanisms by which these risk factors influence Alzheimer’s risk remain incompletely understood. Genomic structural equation modelling can reveal patterns of shared genetic architecture that provide insight into the pathophysiology of complex traits.MethodsWe identified genome-wide association studies for Alzheimer’s disease and its major modifiable risk factors: less education, hearing loss, hypertension, high alcohol intake, obesity, smoking, depression, social isolation, physical inactivity, type 2 diabetes, sleep disturbance and socioeconomic deprivation. We performed linkage disequilibrium score regression among these traits, followed by exploratory factor analysis, confirmatory factor analysis and structural equation modelling.ResultsWe identified complex networks of linkage disequilibrium among Alzheimer’s disease risk factors. The data were best explained by a bi-factor model, incorporating a Common Factor for Alzheimer’s risk, and three orthogonal sub-clusters of risk factors, which were validated across the two halves of the autosome. The first sub-cluster was characterised by risk factors related to sedentary lifestyle behaviours, the second by traits associated with reduced life expectancy and the third by traits that are possible prodromes of Alzheimer’s disease. Alzheimer’s disease was more genetically distinct and displayed minimal shared genetic architecture with its risk factors, which was robust to the exclusion of APOE.ConclusionShared genetic architecture may contribute to epidemiological associations between Alzheimer’s disease and its risk factors. Understanding the biology reflected by this communality may provide novel mechanistic insights that could help to prioritise targets for dementia prevention.

scholarly journals Are Genes Destiny? Exploring the Role of Intrauterine Environment in Moderating Genetic Influences on Body Weight

2017 ◽  
Author(s):  
Jinho Kim
Keyword(s):  
Birth Weight ◽  
Environmental Factors ◽  
In Utero ◽  
Genetic Effects ◽  
Interactive Effects ◽  
Environment Interaction ◽  
Intrauterine Environment ◽  
Fetal Origins ◽  
Gene Environment Interaction ◽  
Gene Environment

By incorporating molecular genetic variants and the fetal origins of obesity hypothesis into a gene-environment interaction framework, this study investigates the potential interactive effects of variation in the obesity-associated gene (FTO) and intrauterine environment on body mass index (BMI) in adulthood. This study draws on data from the Wisconsin Longitudinal Study, and uses sibling comparisons that allow for quasi-experimental variations in both genetic and environmental factors. Findings demonstrated that even after controlling for unobserved family background, the FTO variants and birth weight are generally associated with adult BMI. Moreover, this study found that the effects of having a risk allele of the FTO gene are largely concentrated on those who were heavier at birth, providing evidence for a gene-environment interaction on BMI and the development of obesity. Results of this study suggest that genes are not destiny and environmental factors may offset the effects of obesity-promoting genes. In particular, efforts to counteract genetic effects on obesity may begin as early as in utero. Interventions to prevent higher birth weight may help reduce the risk of obesity later in life, by directly addressing the programming effects of the in utero environment and also indirectly moderating the obesity-promoting genetic effects.

scholarly journals Mental health, disability and cardiovascular risks in South African adults with hypertension: structural equation models of causal pathways

2020 ◽  
Author(s):  
Max Oscar Bachmann ◽  
Arvin Bhana ◽  
Katherine Grady ◽  
Naomi Folb ◽  
Graham Thornicroft ◽  
...  
Keyword(s):  
Mental Health ◽  
Myocardial Infarction ◽  
Blood Pressure ◽  
South African ◽  
Indirect Effects ◽  
Structural Equation ◽  
Depression Symptoms ◽  
Cardiovascular Risks ◽  
Causal Pathways ◽  
One Year

Abstract Aim South African adults with hypertension often have comorbid physical and mental health problems and disabilities, which can influence each other in complex ways. We modelled potential causal pathways connecting multimorbidity, depression, stress, disability and cardiovascular risks. Methods The study analysed observational data on 1043 adults with treated hypertension and with symptoms of depression (Patient Health Questionnaire-9 score > 9) who participated in a randomised trial in 20 primary health care clinics. A structural equation path model using cross-sectional baseline data estimated direct and indirect effects of sociodemographic variables and comorbidities on depression, stress and disability scores, and their further direct and indirect effects on smoking, body mass index and blood pressure. A cross-lagged structural equation model using longitudinal data estimated effects of depression symptoms, disability and blood pressure on each other over time. Results At baseline, depression symptoms as outcome were positively associated with previous myocardial infarction, blood pressure, and disability. Disability was positively associated with depression symptoms, stress scores, myocardial infarction and tuberculosis. Body mass index was positively associated with income and female sex and negatively associated with HIV, tuberculosis, perceived stress and age. Systolic blood pressure was positively associated with depression symptoms and age, and negatively associated with tuberculosis. Indirect effects of myocardial infarction and age on disability were partly mediated through perceived stress and depression symptoms. Baseline depression symptoms predicted greater disability after one year, and baseline disability predicted greater depression symptoms and higher blood pressure after one year. Conclusions Control of cardiovascular risk factors in primary care patients with hypertension is interrelated with their mental health, disability, and comorbidity. Better mental health care and management of disability could help control blood pressure and reduce cardiovascular risk.

The role of very low birth weight and prematurity on cardiovascular disease risk and on kidney development in children: a pilot study

2020 ◽  
Vol 72 (3) ◽  
Author(s):  
Marco M. Ciccone ◽  
Francesca Cortese ◽  
Michele Gesualdo ◽  
Antonio Di Mauro ◽  
Silvio Tafuri ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Birth Weight ◽  
Pilot Study ◽  
Low Birth Weight ◽  
Kidney Development ◽  
Very Low Birth Weight ◽  
Disease Risk ◽  
Cardiovascular Disease Risk
Sign in / Sign up

Export Citation Format

Share Document