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This article is original by Translational Medicine Network.
Please indicate the source for reprinting.
Author: Liz Zee Guide: Central obesity is a disease that poses a major risk to global health and requires new scientific methods to be explored
.
The purpose of this study is to use DNA methylation analysis to detect DNA methylation sites associated with the obese phenotype
.
A research team published its findings in "BMC Medical Genomics".
The paper is titled "Epigenome-wide association study detects a novel loci associated with central obesity in healthy subjects".
Epigenetic variants are cytosine bases, histones and The covalent modification of nucleosome location changes can regulate the influence of genotype on specific phenotypes, thereby affecting the physiological mechanism and the pathophysiology of many diseases
.
One of the most widely studied is cytosine methylation, which is a covalent attachment of methyl groups to DNA sequences, which usually leads to gene silencing in methylated regions
.
DNA methylation patterns are not static, but undergo precise and highly coordinated changes.
These changes can be mediated by environmental and genetic factors and inherited through cell mitosis
.
This process has already occurred during embryo formation and is essential for development, differentiation and cell variability, as well as the transcriptional regulation of genes and miRNAs
.
On the other hand, the atypical pattern of DNA methylation is related to obesity, oxidative stress, hypertension, inflammation, angiogenesis, and other pathological processes related to the development of chronic diseases
.
Obesity is a systemic disease and a growing health problem, which increases the risk of many common diseases
.
Excessive adipose tissue can cause chronic low-grade inflammation, which is related to immune activation and oxidative stress, insulin resistance, high blood pressure and dyslipidemia
.
The most common method for determining general obesity is the body mass index (BMI), which is the ratio of an individual's mass (weight) to height, in kg/m²
.
However, clinical evidence suggests that diseases like diabetes are more closely linked to central obesity (the part where visceral fat tissue is stored)
.
Therefore, waist circumference (WC) and waist-to-hip ratio can well explain obesity-related diseases
.
The increase in the prevalence of obesity worldwide is mainly due to changes in the environment, and a person's genes are considered to be one of the main reasons for differences in susceptibility to weight gain
.
The high heritability of this phenotype has been confirmed in several epidemiological studies and genome-wide association studies (GWAS), in which 27% to 30% of the total BMI variance is consistent with common single nucleotide polymorphisms (SNPs) Related
.
In addition, the obesity environment during uterine development and early childhood is associated with an increased risk of developing a series of chronic diseases in adulthood, which indicates that early environmental effects can cause permanent effects
.
This interaction between biological and environmental factors is believed to be mediated by epigenetic mechanisms.
Through epigenetic mechanisms, environmental factors can change gene expression, which explains the rising prevalence of obesity in the past few decades
.
Epigenome-wide association analysis (EWAS) provides the possibility for in-depth understanding of epigenetic changes
.
Research on DNA methylation through multiple EWAS to determine the common variation of DNA methylome related to obesity phenotype, and pointed out several sites of HIF3A, ABCG1 and CPT1A
.
In order to further promote the understanding of obesity characteristics, in this study, the researchers detected the methylation levels associated with central obesity in healthy people, measured by WC and waist-to-hip ratio adjusted according to BMI
.
Detection of healthy individuals can avoid the differences caused by extreme obesity and the existence of accompanying diseases in specific populations
.
The researchers' findings provide new insights into the genetic regulation of visceral fat accumulation and propose a new variant that may increase susceptibility to chronic diseases
.
The study looked at 210 health-related persons from 73 families in the STANISLAS Family Study (SFS), including 115 adults and 95 children
.
SFS is a 10-year longitudinal cohort study, including three follow-ups every 5 years
.
The study involved 1,006 French families from Vandoeuvre-lès-Nancy who were initially recruited between 1993 and 1995
.
All subjects are European Caucasians and have no chronic diseases (CVD, cancer, diabetes, hypertension, etc.
)
.
The research protocol has been approved by the Institutional Ethics Committee, and all subjects have agreed in writing to participate in this research
.
For participants under the age of 18, their parents also agreed to participate
.
Collect data and blood samples during the SFS baseline visit
.
All clinical indicators are measured in the laboratory of Vandoeuvre lès Nancy Preventive Medicine Center in France
.
BMI is calculated using the Quetelet index formula, that is, weight (kg) divided by height² (m²)
.
The criteria for obesity are: adult BMI ≥ 30 kg/m², child BMI ≥ the corresponding age of the French BMI curve and the 97th percentile of gender
.
Studies have found that insufficient expression of gangliosides in hypothalamic neurons can cause neuronal leptin and insulin signals to be imbalanced, thereby affecting body weight regulation and energy homeostasis
.
Gangliosides interact with molecules in signal transduction pathways, such as receptor tyrosine kinases (RTKs)
.
Changes in the composition of gangliosides induce the separation of RTKs from the microdomains rich in glycolipids, thereby reducing receptor phosphorylation and causing insulin resistance
.
Therefore, insulin is an important regulator of adipocyte biology, and insulin receptor resistance is one of the important causes of obesity and one of the biggest contributors to the development of obesity
.
Although the above-mentioned methylation regulates the influence mechanism on WC through insulin, it cannot be ruled out that methylation may be the result of WC changes rather than the cause
.
In fact, a meta-analysis by S.
Wahl et al.
showed that mutations in DNA methylation are usually the result of obesity
.
Therefore, specific molecular mechanisms may make it possible to methylate the regulatory regions of genes related to obesity, but the exact mechanism of this regulation remains to be elucidated
.
Epigenetic studies on the obesity phenotype of healthy individuals have been conducted before, however, as far as we know, this is the only EWAS study that includes only healthy subjects
.
Later analysis showed that the statistical verification power of the research results is very high (100%)
.
However, it needs to be said that the researchers also analyzed separate children and adult populations and found no significant associations, which may be due to the reduced effectiveness of the smaller samples analyzed separately
.
The researchers also conducted a separate analysis by gender, and there was no significant difference
.
One limitation of the study is the small sample size
.
Although researchers have determined a result with high statistical power, it is impossible for researchers to use it in population-specific studies
.
Since epigenetic changes can be tissue-specific, the limitation of this study is also the use of blood samples without tissue-specific replication
.
Although the intra-subject correlation of specific sites of CpG in blood and adipose tissue has been confirmed before, the use of methylation markers in blood to reflect the corresponding characteristics in target tissues still requires caution
.
The study found a new connection between DNA methylation and WC
.
This indicates that the epigenetic mechanism may have a significant impact on the waist circumference ratio of healthy people
.
Further research is necessary to resolve the causality of this association
.
Reference materials: https://bmcmedgenomics.
biomedcentral.
com/articles/10.
1186/s12920-021-01077-9#abbreviations Note: This article aims to introduce medical research progress and cannot be used as a reference for treatment options
.
If you need health guidance, please go to a regular hospital
.
Popular·Article Gene Sequencing [Hot Discussion] How to achieve more uniform and accurate genetic testing? Shock! Two top genetic testing companies performed liquid biopsies on the same group of cancer patients, and the results were quite different.
The new coronavirus [Nature Hot Discussion] The new coronavirus is getting more and more powerful, but the protective efficacy of the vaccine is gradually weakening.
What should we do? New Coronavirus [Nature Hot Discussion] The epidemic in Fujian has spread to four places! Israel’s 1.
1 million large-scale study: The vaccinated booster shot is 19.
5 times less likely to be infected with the new crown than people who have only received two injections.
[Science] Nearly 500 million people live in areas where the coronavirus may overflow.
The new crown is just the tip of the iceberg.
There will be more SARS-like viruses! Gut microbes [Genome Medicine] is the first to use gut microbial data for the prognosis study of rheumatoid arthritis, which is expected to become the key to future treatment! Organoid Research [Nature Sub-Journal] The use of synthetic new gels can easily cultivate pancreatic "organoids" and accurately replicate human pancreatic tumor research [The Lancet] Low-dose CT screening for lung cancer can really effectively reduce mortality NS? British scientists will show you the answer through experiments! New crown virus [heavy weight] How protective is the new crown vaccine against delta virus? The US Centers for Disease Control and Prevention has given the answer: The death rate of the unvaccinated population is 11 times that of the vaccinated population! Gene Sequencing [Nature Sub-Journal] The largest DNAm gene study to date: the study of genetic mutations related to DNAm at 420,509 DNAm loci in the blood has been identified.
[Heavyweight] Johns Hopkins University scientists have discovered genetic The self-correction function can resist blood cancer, which is expected to be a major breakthrough in the treatment of blood cancer! Genetic testing [Nature Sub-Journal] The 1.
5 million largest genome-wide association study has identified nearly 600 gene loci related to anti-social behavior, alcoholism, and opioid addiction.
The new coronavirus [Nature] is a heavyweight! Why can the delta mutant virus spread so quickly and fiercely? Scientists from the University of Cambridge will take you through its recommendations and activities The 3rd Shanghai International Cancer Conference The 5th Symposium on Modern Clinical Molecular Diagnosis
Please indicate the source for reprinting.
Author: Liz Zee Guide: Central obesity is a disease that poses a major risk to global health and requires new scientific methods to be explored
.
The purpose of this study is to use DNA methylation analysis to detect DNA methylation sites associated with the obese phenotype
.
A research team published its findings in "BMC Medical Genomics".
The paper is titled "Epigenome-wide association study detects a novel loci associated with central obesity in healthy subjects".
Epigenetic variants are cytosine bases, histones and The covalent modification of nucleosome location changes can regulate the influence of genotype on specific phenotypes, thereby affecting the physiological mechanism and the pathophysiology of many diseases
.
One of the most widely studied is cytosine methylation, which is a covalent attachment of methyl groups to DNA sequences, which usually leads to gene silencing in methylated regions
.
DNA methylation patterns are not static, but undergo precise and highly coordinated changes.
These changes can be mediated by environmental and genetic factors and inherited through cell mitosis
.
This process has already occurred during embryo formation and is essential for development, differentiation and cell variability, as well as the transcriptional regulation of genes and miRNAs
.
On the other hand, the atypical pattern of DNA methylation is related to obesity, oxidative stress, hypertension, inflammation, angiogenesis, and other pathological processes related to the development of chronic diseases
.
Obesity is a systemic disease and a growing health problem, which increases the risk of many common diseases
.
Excessive adipose tissue can cause chronic low-grade inflammation, which is related to immune activation and oxidative stress, insulin resistance, high blood pressure and dyslipidemia
.
The most common method for determining general obesity is the body mass index (BMI), which is the ratio of an individual's mass (weight) to height, in kg/m²
.
However, clinical evidence suggests that diseases like diabetes are more closely linked to central obesity (the part where visceral fat tissue is stored)
.
Therefore, waist circumference (WC) and waist-to-hip ratio can well explain obesity-related diseases
.
The increase in the prevalence of obesity worldwide is mainly due to changes in the environment, and a person's genes are considered to be one of the main reasons for differences in susceptibility to weight gain
.
The high heritability of this phenotype has been confirmed in several epidemiological studies and genome-wide association studies (GWAS), in which 27% to 30% of the total BMI variance is consistent with common single nucleotide polymorphisms (SNPs) Related
.
In addition, the obesity environment during uterine development and early childhood is associated with an increased risk of developing a series of chronic diseases in adulthood, which indicates that early environmental effects can cause permanent effects
.
This interaction between biological and environmental factors is believed to be mediated by epigenetic mechanisms.
Through epigenetic mechanisms, environmental factors can change gene expression, which explains the rising prevalence of obesity in the past few decades
.
Epigenome-wide association analysis (EWAS) provides the possibility for in-depth understanding of epigenetic changes
.
Research on DNA methylation through multiple EWAS to determine the common variation of DNA methylome related to obesity phenotype, and pointed out several sites of HIF3A, ABCG1 and CPT1A
.
In order to further promote the understanding of obesity characteristics, in this study, the researchers detected the methylation levels associated with central obesity in healthy people, measured by WC and waist-to-hip ratio adjusted according to BMI
.
Detection of healthy individuals can avoid the differences caused by extreme obesity and the existence of accompanying diseases in specific populations
.
The researchers' findings provide new insights into the genetic regulation of visceral fat accumulation and propose a new variant that may increase susceptibility to chronic diseases
.
The study looked at 210 health-related persons from 73 families in the STANISLAS Family Study (SFS), including 115 adults and 95 children
.
SFS is a 10-year longitudinal cohort study, including three follow-ups every 5 years
.
The study involved 1,006 French families from Vandoeuvre-lès-Nancy who were initially recruited between 1993 and 1995
.
All subjects are European Caucasians and have no chronic diseases (CVD, cancer, diabetes, hypertension, etc.
)
.
The research protocol has been approved by the Institutional Ethics Committee, and all subjects have agreed in writing to participate in this research
.
For participants under the age of 18, their parents also agreed to participate
.
Collect data and blood samples during the SFS baseline visit
.
All clinical indicators are measured in the laboratory of Vandoeuvre lès Nancy Preventive Medicine Center in France
.
BMI is calculated using the Quetelet index formula, that is, weight (kg) divided by height² (m²)
.
The criteria for obesity are: adult BMI ≥ 30 kg/m², child BMI ≥ the corresponding age of the French BMI curve and the 97th percentile of gender
.
Studies have found that insufficient expression of gangliosides in hypothalamic neurons can cause neuronal leptin and insulin signals to be imbalanced, thereby affecting body weight regulation and energy homeostasis
.
Gangliosides interact with molecules in signal transduction pathways, such as receptor tyrosine kinases (RTKs)
.
Changes in the composition of gangliosides induce the separation of RTKs from the microdomains rich in glycolipids, thereby reducing receptor phosphorylation and causing insulin resistance
.
Therefore, insulin is an important regulator of adipocyte biology, and insulin receptor resistance is one of the important causes of obesity and one of the biggest contributors to the development of obesity
.
Although the above-mentioned methylation regulates the influence mechanism on WC through insulin, it cannot be ruled out that methylation may be the result of WC changes rather than the cause
.
In fact, a meta-analysis by S.
Wahl et al.
showed that mutations in DNA methylation are usually the result of obesity
.
Therefore, specific molecular mechanisms may make it possible to methylate the regulatory regions of genes related to obesity, but the exact mechanism of this regulation remains to be elucidated
.
Epigenetic studies on the obesity phenotype of healthy individuals have been conducted before, however, as far as we know, this is the only EWAS study that includes only healthy subjects
.
Later analysis showed that the statistical verification power of the research results is very high (100%)
.
However, it needs to be said that the researchers also analyzed separate children and adult populations and found no significant associations, which may be due to the reduced effectiveness of the smaller samples analyzed separately
.
The researchers also conducted a separate analysis by gender, and there was no significant difference
.
One limitation of the study is the small sample size
.
Although researchers have determined a result with high statistical power, it is impossible for researchers to use it in population-specific studies
.
Since epigenetic changes can be tissue-specific, the limitation of this study is also the use of blood samples without tissue-specific replication
.
Although the intra-subject correlation of specific sites of CpG in blood and adipose tissue has been confirmed before, the use of methylation markers in blood to reflect the corresponding characteristics in target tissues still requires caution
.
The study found a new connection between DNA methylation and WC
.
This indicates that the epigenetic mechanism may have a significant impact on the waist circumference ratio of healthy people
.
Further research is necessary to resolve the causality of this association
.
Reference materials: https://bmcmedgenomics.
biomedcentral.
com/articles/10.
1186/s12920-021-01077-9#abbreviations Note: This article aims to introduce medical research progress and cannot be used as a reference for treatment options
.
If you need health guidance, please go to a regular hospital
.
Popular·Article Gene Sequencing [Hot Discussion] How to achieve more uniform and accurate genetic testing? Shock! Two top genetic testing companies performed liquid biopsies on the same group of cancer patients, and the results were quite different.
The new coronavirus [Nature Hot Discussion] The new coronavirus is getting more and more powerful, but the protective efficacy of the vaccine is gradually weakening.
What should we do? New Coronavirus [Nature Hot Discussion] The epidemic in Fujian has spread to four places! Israel’s 1.
1 million large-scale study: The vaccinated booster shot is 19.
5 times less likely to be infected with the new crown than people who have only received two injections.
[Science] Nearly 500 million people live in areas where the coronavirus may overflow.
The new crown is just the tip of the iceberg.
There will be more SARS-like viruses! Gut microbes [Genome Medicine] is the first to use gut microbial data for the prognosis study of rheumatoid arthritis, which is expected to become the key to future treatment! Organoid Research [Nature Sub-Journal] The use of synthetic new gels can easily cultivate pancreatic "organoids" and accurately replicate human pancreatic tumor research [The Lancet] Low-dose CT screening for lung cancer can really effectively reduce mortality NS? British scientists will show you the answer through experiments! New crown virus [heavy weight] How protective is the new crown vaccine against delta virus? The US Centers for Disease Control and Prevention has given the answer: The death rate of the unvaccinated population is 11 times that of the vaccinated population! Gene Sequencing [Nature Sub-Journal] The largest DNAm gene study to date: the study of genetic mutations related to DNAm at 420,509 DNAm loci in the blood has been identified.
[Heavyweight] Johns Hopkins University scientists have discovered genetic The self-correction function can resist blood cancer, which is expected to be a major breakthrough in the treatment of blood cancer! Genetic testing [Nature Sub-Journal] The 1.
5 million largest genome-wide association study has identified nearly 600 gene loci related to anti-social behavior, alcoholism, and opioid addiction.
The new coronavirus [Nature] is a heavyweight! Why can the delta mutant virus spread so quickly and fiercely? Scientists from the University of Cambridge will take you through its recommendations and activities The 3rd Shanghai International Cancer Conference The 5th Symposium on Modern Clinical Molecular Diagnosis
