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Nutrients Mar 2024Both genetics and vitamin D deficiency are associated with childhood obesity. However, the role of vitamin D status between polygenic and childhood obesity has been...
BACKGROUND
Both genetics and vitamin D deficiency are associated with childhood obesity. However, the role of vitamin D status between polygenic and childhood obesity has been unknown. The current study aimed to determine the relation between genetic factors, vitamin D status, and BMI-for-age score (zBMI) in Chinese preschool children.
METHODS
A total of 1046 participants aged 3.7 to 6.6 years old from the Long-term Health Effects Assessment Project of Infants and Toddlers Nutritional Pack (LHEAPITNP) were included in this study. The polygenic risk score (PRS) was established based on 55 BMI-related single nucleotide polymorphisms (SNPs) derived from a published genome-wide association study (GWAS) for BMI. Serum 25(OH)D was used as an index of vitamin D status and measured with liquid chromatography-tandem mass spectrometry (LC/MS-MS) assay. The Wilcoxon test or Kruskal-Wallis test was used to compare the differences of variables between different groups and Spearman correlation analysis was used for analyzing the correlations between the PRS, 25(OH)D levels, and zBMI.
RESULTS
The PRS showed a positive relation to zBMI ( = 0.0953, = 0.0022) and 25(OH)D showed a negative relation to zBMI ( = -0.1082, = 0.0005) in the full-adjustment model. In addition, the differences in zBMI at different vitamin D statuses in the low-risk PRS group and the intermediate-risk PRS group were both statistically significant ( = 0.0308, = 0.0121), the median zBMI was both higher at vitamin D insufficiency status. And the difference in zBMI between different genetic risk groups was also statistically significant at vitamin D sufficiency status ( = 0.0077). Furthermore, genetic risk showed a positive relation to zBMI at vitamin D sufficiency status, and the for trend was 0.0028.
CONCLUSIONS
Our findings suggested that vitamin D was related to zBMI negatively in Chinese preschoolers and maintaining adequate vitamin D levels may only contribute to lower the zBMI in preschoolers with low and intermediate genetic susceptibility.
Topics: Child; Infant; Humans; Child, Preschool; Vitamin D; Pediatric Obesity; Body Mass Index; Genetic Risk Score; Genome-Wide Association Study; Vitamin D Deficiency; China
PubMed: 38542703
DOI: 10.3390/nu16060792 -
JAMA Network Open Mar 2024Despite consistent public health recommendations, obesity rates in the US continue to increase. Physical activity recommendations do not account for individual genetic...
IMPORTANCE
Despite consistent public health recommendations, obesity rates in the US continue to increase. Physical activity recommendations do not account for individual genetic variability, increasing risk of obesity.
OBJECTIVE
To use activity, clinical, and genetic data from the All of Us Research Program (AoURP) to explore the association of genetic risk of higher body mass index (BMI) with the level of physical activity needed to reduce incident obesity.
DESIGN, SETTING, AND PARTICIPANTS
In this US population-based retrospective cohort study, participants were enrolled in the AoURP between May 1, 2018, and July 1, 2022. Enrollees in the AoURP who were of European ancestry, owned a personal activity tracking device, and did not have obesity up to 6 months into activity tracking were included in the analysis.
EXPOSURE
Physical activity expressed as daily step counts and a polygenic risk score (PRS) for BMI, calculated as weight in kilograms divided by height in meters squared.
MAIN OUTCOME AND MEASURES
Incident obesity (BMI ≥30).
RESULTS
A total of 3124 participants met inclusion criteria. Among 3051 participants with available data, 2216 (73%) were women, and the median age was 52.7 (IQR, 36.4-62.8) years. The total cohort of 3124 participants walked a median of 8326 (IQR, 6499-10 389) steps/d over a median of 5.4 (IQR, 3.4-7.0) years of personal activity tracking. The incidence of obesity over the study period increased from 13% (101 of 781) to 43% (335 of 781) in the lowest and highest PRS quartiles, respectively (P = 1.0 × 10-20). The BMI PRS demonstrated an 81% increase in obesity risk (P = 3.57 × 10-20) while mean step count demonstrated a 43% reduction (P = 5.30 × 10-12) when comparing the 75th and 25th percentiles, respectively. Individuals with a PRS in the 75th percentile would need to walk a mean of 2280 (95% CI, 1680-3310) more steps per day (11 020 total) than those at the 50th percentile to have a comparable risk of obesity. To have a comparable risk of obesity to individuals at the 25th percentile of PRS, those at the 75th percentile with a baseline BMI of 22 would need to walk an additional 3460 steps/d; with a baseline BMI of 24, an additional 4430 steps/d; with a baseline BMI of 26, an additional 5380 steps/d; and with a baseline BMI of 28, an additional 6350 steps/d.
CONCLUSIONS AND RELEVANCE
In this cohort study, the association between daily step count and obesity risk across genetic background and baseline BMI were quantified. Population-based recommendations may underestimate physical activity needed to prevent obesity among those at high genetic risk.
Topics: Female; Humans; Middle Aged; Male; Cohort Studies; Retrospective Studies; Population Health; Obesity; Exercise; Genetic Risk Score
PubMed: 38536175
DOI: 10.1001/jamanetworkopen.2024.3821 -
Therapeutic Advances in Respiratory... 2024Prior pulmonary tuberculosis (PTB) might be associated with the development of chronic obstructive pulmonary disease (COPD). However, the impact of prior PTB on the risk...
BACKGROUND
Prior pulmonary tuberculosis (PTB) might be associated with the development of chronic obstructive pulmonary disease (COPD). However, the impact of prior PTB on the risk of incident COPD has not been studied in a large prospective cohort study of the European population.
OBJECTIVES
This study aimed to investigate the association of prior PTB with the risk of COPD.
DESIGN
Prospective cohort study.
METHODS
A multivariable Cox proportional model was used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) for the association of prior PTB with COPD. Subgroup analyses were further conducted among individuals stratified by age, sex, body mass index, smoking status, drinking status, physical activity, and polygenic risk score (PRS).
RESULTS
The study involved a total of 216,130 participants, with a median follow-up period of 12.6 years and 2788 incident cases of COPD. Individuals with a prior history of PTB at baseline had an 87% higher risk of developing incident COPD compared to those without such history [adjusted hazard ratio (aHR) = 1.87; 95% confidence interval (CI): 1.26-2.77; = 0.002]. Subgroup analysis revealed that individuals having prior PTB history presented a higher risk of incident COPD among individuals who were aged from 50 to 59 years with aHR of 2.47 (1.02-5.95, = 0.044), older than 59 years with aHR of 1.81 (1.16-2.81, = 0.008), male with aHR of 2.37 (1.47-3.83, < 0.001), obesity with aHR of 3.35 (2.16-5.82, < 0.001), previous smoking with aHR of 2.27 (1.39-3.72, < 0.001), current drinking with aHR of 1.98 (1.47-3.83, < 0.001), low physical activity with aHR of 2.62 (1.30-5.26, = 0.007), and low PRS with aHR of 3.24 (1.61-6.53, < 0.001), as well as high PRS with aHR of 2.43 (1.15-5.14, = 0.019).
CONCLUSION
A history of PTB is an important independent risk factor for COPD. Clinical staff should be aware of this risk factor in patients with prior PTB, particularly in countries or regions with high burdens of PTB.
Topics: Humans; Male; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Tuberculosis, Pulmonary; Risk Factors; Smoking
PubMed: 38529640
DOI: 10.1177/17534666241239455 -
International Journal of Cardiology Jun 2024Current risk assessment for ischemic stroke (IS) is limited to clinical variables. We hypothesize that polygenic scores (PGS) of IS (PGS) and IS-associated diseases such...
BACKGROUND
Current risk assessment for ischemic stroke (IS) is limited to clinical variables. We hypothesize that polygenic scores (PGS) of IS (PGS) and IS-associated diseases such as atrial fibrillation (AF), venous thromboembolism (VTE), coronary artery disease (CAD), hypertension (HTN), and Type 2 diabetes (T2D) may improve the performance of IS risk assessment.
METHODS
Incident IS was followed for 479,476 participants in the UK Biobank who did not have an IS diagnosis prior to the recruitment. Lifestyle variables (obesity, smoking and alcohol) at the time of study recruitment, clinical diagnoses of IS-associated diseases, PGS, and five PGSs for IS-associated diseases were tested using the Cox proportional-hazards model. Predictive performance was assessed using the C-statistic and net reclassification index (NRI).
RESULTS
During a median average 12.5-year follow-up, 8374 subjects were diagnosed with IS. Known clinical variables (age, gender, clinical diagnoses of IS-associated diseases, obesity, and smoking) and PGS were all independently associated with IS (P < 0.001). In addition, PGS and each PGS for IS-associated diseases was also independently associated with IS (P < 0.001). Compared to the clinical model, a joint clinical/PGS model improved the C-statistic for predicting IS from 0.71 to 0.73 (P < 0.001) and significantly reclassified IS risk (NRI = 0.017, P < 0.001), and 6.48% of subjects were upgraded from low to high risk.
CONCLUSIONS
Adding PGSs of IS and IS-associated diseases to known clinical risk factors statistically improved risk assessment for IS, demonstrating the supplementary value of inherited susceptibility measurement . However, its clinical utility is likely limited due to modest improvements in predictive values.
Topics: Humans; Ischemic Stroke; Stroke; Diabetes Mellitus, Type 2; Risk Factors; Risk Assessment; Atrial Fibrillation; Obesity
PubMed: 38521508
DOI: 10.1016/j.ijcard.2024.131990 -
BMC Medicine Mar 2024Sarcopenic obesity, a clinical and functional condition characterized by the coexistence of obesity and sarcopenia, has not been investigated in relation to dementia...
BACKGROUND
Sarcopenic obesity, a clinical and functional condition characterized by the coexistence of obesity and sarcopenia, has not been investigated in relation to dementia risk and its onset.
METHODS
We included 208,867 participants from UK biobank, who aged 60 to 69 years at baseline. Dementia diagnoses were identified using hospital records and death register data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models to evaluate the associations of obesity, sarcopenia, and sarcopenic obesity with dementia risk, stratified by sex. Stratified analyses were performed across dementia-related polygenic risk score (PRS). Restricted mean survival time models were established to estimate the difference and 95%CIs of dementia onset across different status. Additionally, linear regression models were employed to estimate associations of different status with brain imaging parameters. The mediation effects of chronic diseases were also examined.
RESULTS
Obese women with high PRS had a decreased risk (HR = 0.855 [0.761-0.961]), but obese men with low PRS had an increased risk (HR = 1.223 [1.045-1.431]). Additionally, sarcopenia was associated with elevated dementia risk (HR = 1.323 [1.064-1.644]; HR = 2.144 [1.753-2.621]) in those with low PRS. Among those with high PRS, however, the association was only significant in early-life (HR = 1.679 [1.355-2.081]; HR = 2.069 [1.656-2.585]). Of note, sarcopenic obesity was associated with higher dementia risk (HR = 1.424 [1.227-1.653]; HR = 1.989 [1.702-2.323]), and results remained similar stratified by PRS. Considering dementia onset, obesity was associated with dementia by 1.114 years delayed in women, however, 0.170 years advanced in men. Sarcopenia (women: 0.080 years; men: 0.192 years) and sarcopenic obesity (women: 0.109 years; men: 0.511 years) respectively advanced dementia onset. Obesity, sarcopenia, and sarcopenic obesity were respectively related to alterations in different brain regions. Association between sarcopenic obesity and dementia was mediated by chronic diseases.
CONCLUSIONS
Sarcopenic obesity and sarcopenia were respectively associated with increased dementia risk and advanced dementia onset to vary degree. The role of obesity in dementia may differ by sex and genetic background.
Topics: Male; Humans; Female; Sarcopenia; Cohort Studies; Obesity Paradox; Obesity; Genetic Risk Score; Chronic Disease; Dementia
PubMed: 38520024
DOI: 10.1186/s12916-024-03357-4 -
JAMA Network Open Mar 2024Body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is a commonly used estimate of obesity, which is a complex trait affected by...
IMPORTANCE
Body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is a commonly used estimate of obesity, which is a complex trait affected by genetic and lifestyle factors. Marked weight gain and loss could be associated with adverse biological processes.
OBJECTIVE
To evaluate the association between BMI variability and incident cardiovascular disease (CVD) events in 2 distinct cohorts.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used data from the Million Veteran Program (MVP) between 2011 and 2018 and participants in the UK Biobank (UKB) enrolled between 2006 and 2010. Participants were followed up for a median of 3.8 (5th-95th percentile, 3.5) years. Participants with baseline CVD or cancer were excluded. Data were analyzed from September 2022 and September 2023.
EXPOSURE
BMI variability was calculated by the retrospective SD and coefficient of variation (CV) using multiple clinical BMI measurements up to the baseline.
MAIN OUTCOMES AND MEASURES
The main outcome was incident composite CVD events (incident nonfatal myocardial infarction, acute ischemic stroke, and cardiovascular death), assessed using Cox proportional hazards modeling after adjustment for CVD risk factors, including age, sex, mean BMI, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking status, diabetes status, and statin use. Secondary analysis assessed whether associations were dependent on the polygenic score of BMI.
RESULTS
Among 92 363 US veterans in the MVP cohort (81 675 [88%] male; mean [SD] age, 56.7 [14.1] years), there were 9695 Hispanic participants, 22 488 non-Hispanic Black participants, and 60 180 non-Hispanic White participants. A total of 4811 composite CVD events were observed from 2011 to 2018. The CV of BMI was associated with 16% higher risk for composite CVD across all groups (hazard ratio [HR], 1.16; 95% CI, 1.13-1.19). These associations were unchanged among subgroups and after adjustment for the polygenic score of BMI. The UKB cohort included 65 047 individuals (mean [SD] age, 57.30 (7.77) years; 38 065 [59%] female) and had 6934 composite CVD events. Each 1-SD increase in BMI variability in the UKB cohort was associated with 8% increased risk of cardiovascular death (HR, 1.08; 95% CI, 1.04-1.11).
CONCLUSIONS AND RELEVANCE
This cohort study found that among US veterans, higher BMI variability was a significant risk marker associated with adverse cardiovascular events independent of mean BMI across major racial and ethnic groups. Results were consistent in the UKB for the cardiovascular death end point. Further studies should investigate the phenotype of high BMI variability.
Topics: Female; Male; Humans; Middle Aged; Body Mass Index; Ischemic Stroke; Cohort Studies; Retrospective Studies; Myocardial Infarction; Cholesterol, HDL
PubMed: 38512255
DOI: 10.1001/jamanetworkopen.2024.3062 -
Diabetes, Obesity & Metabolism Apr 2024Over the past few decades, there has been a global surge in the prevalence of obesity, rendering it a globally recognized epidemic. Contrary to simply being a medical...
Over the past few decades, there has been a global surge in the prevalence of obesity, rendering it a globally recognized epidemic. Contrary to simply being a medical condition, obesity is an intricate disease with a multifactorial aetiology. Understanding the precise cause of obesity remains a challenge; nevertheless, there seems to be a complex interplay among biological, psychosocial and behavioural factors. Studies on the genetic factors of obesity have revealed several pathways in the brain that play a crucial role in food intake regulation. The best characterized pathway, thus far, is the leptin-melanocortin pathway, from which disruptions are responsible for the majority of monogenic obesity disorders. The effectiveness of conservative lifestyle interventions in addressing monogenic obesity has been limited. Therefore, it is crucial to complement the management strategy with pharmacological and surgical options. Emphasis has been placed on developing drugs aimed at replacing the absent signals, with the goal of restoring the pathway. In both monogenic and polygenic forms of obesity, outcomes differ across various interventions, likely due to the multifaceted nature of the disease. This underscores the need to explore alternative therapeutic strategies that can mitigate this heterogeneity. Precision medicine can be regarded as a powerful tool that can address this concern, as it values the understanding of the underlying abnormality triggering the disease and provides a tailored treatment accordingly. This would assist in optimizing outcomes of the current therapeutic approaches and even aid in the development of novel treatments capable of more effectively managing the global obesity epidemic.
Topics: Humans; Obesity Management; Receptor, Melanocortin, Type 4; Precision Medicine; Obesity; Leptin; Melanocortins
PubMed: 38504134
DOI: 10.1111/dom.15555 -
Genes & Genomics May 2024Analysing genomes of animal model organisms is widely used for understanding the genetic basis of complex traits and diseases, such as obesity, for which only a few...
BACKGROUND
Analysing genomes of animal model organisms is widely used for understanding the genetic basis of complex traits and diseases, such as obesity, for which only a few mouse models exist, however, without their lean counterparts.
OBJECTIVE
To analyse genetic differences in the unique mouse models of polygenic obesity (Fat line) and leanness (Lean line) originating from the same base population and established by divergent selection over more than 60 generations.
METHODS
Genetic variability was analysed using WGS. Variants were identified with GATK and annotated with Ensembl VEP. g.Profiler, WebGestalt, and KEGG were used for GO and pathway enrichment analysis. miRNA seed regions were obtained with miRPathDB 2.0, LncRRIsearch was used to predict targets of identified lncRNAs, and genes influencing adipose tissue amount were searched using the IMPC database.
RESULTS
WGS analysis revealed 6.3 million SNPs, 1.3 million were new. Thousands of potentially impactful SNPs were identified, including within 24 genes related to adipose tissue amount. SNP density was highest in pseudogenes and regulatory RNAs. The Lean line carries SNP rs248726381 in the seed region of mmu-miR-3086-3p, which may affect fatty acid metabolism. KEGG analysis showed deleterious missense variants in immune response and diabetes genes, with food perception pathways being most enriched. Gene prioritisation considering SNP GERP scores, variant consequences, and allele comparison with other mouse lines identified seven novel obesity candidate genes: 4930441H08Rik, Aff3, Fam237b, Gm36633, Pced1a, Tecrl, and Zfp536.
CONCLUSION
WGS revealed many genetic differences between the lines that accumulated over the selection period, including variants with potential negative impacts on gene function. Given the increasing availability of mouse strains and genetic polymorphism catalogues, the study is a valuable resource for researchers to study obesity.
Topics: Animals; Mice; Thinness; Obesity; Genome; Whole Genome Sequencing; Adipose Tissue
PubMed: 38483771
DOI: 10.1007/s13258-024-01507-9 -
International Journal of Obesity (2005) Jul 2024The effects of early life exposures on offspring life-course health are well established. This study assessed whether adding early socio-demographic and perinatal...
BACKGROUND/OBJECTIVES
The effects of early life exposures on offspring life-course health are well established. This study assessed whether adding early socio-demographic and perinatal variables to a model based on polygenic risk score (PRS) improves prediction of obesity risk.
METHODS
We used the Jerusalem Perinatal study (JPS) with data at birth and body mass index (BMI) and waist circumference (WC) measured at age 32. The PRS was constructed using over 2.1M common SNPs identified in genome-wide association study (GWAS) for BMI. Linear and logistic models were applied in a stepwise approach. We first examined the associations between genetic variables and obesity-related phenotypes (e.g., BMI and WC). Secondly, socio-demographic variables were added and finally perinatal exposures, such as maternal pre-pregnancy BMI (mppBMI) and gestational weight gain (GWG) were added to the model. Improvement in prediction of each step was assessed using measures of model discrimination (area under the curve, AUC), net reclassification improvement (NRI) and integrated discrimination improvement (IDI).
RESULTS
One standard deviation (SD) change in PRS was associated with a significant increase in BMI (β = 1.40) and WC (β = 2.45). These associations were slightly attenuated (13.7-14.2%) with the addition of early life exposures to the model. Also, higher mppBMI was associated with increased offspring BMI (β = 0.39) and WC (β = 0.79) (p < 0.001). For obesity (BMI ≥ 30) prediction, the addition of early socio-demographic and perinatal exposures to the PRS model significantly increased AUC from 0.69 to 0.73. At an obesity risk threshold of 15%, the addition of early socio-demographic and perinatal exposures to the PRS model provided a significant improvement in reclassification of obesity (NRI, 0.147; 95% CI 0.068-0.225).
CONCLUSIONS
Inclusion of early life exposures, such as mppBMI and maternal smoking, to a model based on PRS improves obesity risk prediction in an Israeli population-sample.
Topics: Humans; Female; Obesity; Israel; Adult; Pregnancy; Male; Body Mass Index; Risk Factors; Genome-Wide Association Study; Multifactorial Inheritance; Young Adult; Genetic Predisposition to Disease
PubMed: 38472354
DOI: 10.1038/s41366-024-01505-7 -
Nutrients Feb 2024It is unknown whether the impact of high diet quality and physical activity depends on the level of polygenic risk score (PRS) in different ancestries. Our...
It is unknown whether the impact of high diet quality and physical activity depends on the level of polygenic risk score (PRS) in different ancestries. Our cross-sectional study utilized de-identified data from 1987-2010 for self-reported European Americans (n = 6575) and African Americans (n = 1606). The high-risk PRS increased ASCVD risk by 59% (Risk Ratio (RR) = 1.59; 95% Confidence Interval:1.16-2.17) in the highest tertile for African Americans and by 15% (RR = 1.15; 1.13-1.30) and 18% (RR = 1.18; 1.04-1.35) in the second and highest tertiles compared to the lowest tertile in European Americans. Within the highest PRS tertiles, high physical activity-diet combinations (Dietary Approaches to Stop High Blood Pressure (DASH), Mediterranean, or Southern) reduced ASCVD risks by 9% (RR = 0.91; 0.85-0.96) to 15% (RR = 0.85; 0.80-0.90) in European Americans; and by 13% (RR = 0.87; 0.78-0.97) and 18% (RR = 0.82; 0.72-0.95) for DASH and Mediterranean diets, respectively, in African Americans. Top molecular pathways included fructose metabolism and catabolism linked to obesity, insulin resistance, and type 2 diabetes. Additional molecular pathways for African Americans were Vitamin D linked to depression and aging acceleration and death signaling associated with cancer. Effects of high diet quality and high physical activity can counterbalance the influences of genetically high-risk PRSs on ASCVD risk, especially in African Americans.
Topics: Humans; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Risk Factors; Dietary Patterns; Genetic Risk Score; Cross-Sectional Studies; Diet, Mediterranean
PubMed: 38398891
DOI: 10.3390/nu16040567