Related Experiment Videos
Maternal Abdominal Obesity and Hirschsprung's Disease in Offspring: A Two-Sample Mendelian Randomization Study
Yun-Jin Wang1, Yi-Fan Fang2, Si-Qi Xie2
1Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, PR China; Department of Pediatric Surgery, Fujian Maternity and Child Health Hospital, Fuzhou, PR China.
The Journal of Surgical Research
|June 23, 2026
Summary
Elevated pre-pregnancy waist-to-hip ratio adjusted for body mass index (WHRadjBMI) in females may causally increase the risk of Hirschsprung
Area of Science:
- Reproductive Health and Genetics
- Pediatric Disease Etiology
Background:
- Investigating the influence of maternal pre-pregnancy adiposity on offspring congenital conditions.
- Focus on the potential causal link between waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and Hirschsprung's disease (HD).
Purpose of the Study:
- To explore the causal effect of pre-pregnancy WHRadjBMI in females on the risk of Hirschsprung's disease in offspring.
- Utilize Mendelian randomization (MR) to assess this relationship.
Main Methods:
- Employed a two-sample Mendelian randomization (MR) analysis using genome-wide association data for WHRadjBMI and HD.
- Identified significant single nucleotide polymorphisms (SNPs) for female WHRadjBMI as instrumental variables.
- Applied inverse-variance weighted, weighted median, and MR-Egger regression methods for robust causal inference.
Main Results:
- Identified 40 significant SNPs associated with female WHRadjBMI.
- Consistent evidence across methods indicated a positive causal association between higher female WHRadjBMI and increased risk of offspring HD (e.g., OR 7.184 for IVW).
- No significant causal effect of genetic susceptibility to HD on female WHRadjBMI was detected.
Conclusions:
- Mendelian randomization analysis strongly suggests that elevated pre-pregnancy WHRadjBMI in females is a causal risk factor for Hirschsprung's disease in offspring.
- Findings highlight the importance of maternal body composition in fetal development and congenital disease risk.
Related Concept Videos
02:41Lethal Alleles
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
01:35Pedigree Analysis
Overview
02:30Genomic Imprinting and Inheritance
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
01:43Sex-linked Disorders
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
01:21Nondisjunction
Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers. Nondisjunction is common during anaphase I or anaphase II of meiosis. Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold sister...
02:59Animal Mitochondrial Genetics
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...