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Genome-wide Association Studies-GWAS01:11

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Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
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While Mendel’s Law of Segregation states that the two alleles for one gene are separated into different gametes, a different question of how different genes are inherited remains. For example, is the gene for tall plants inherited with the gene for green peas? Mendel asked this question by experimenting with a dihybrid cross; a cross in which both parents are homozygous for two distinct traits resulting in an F1 generation that are heterozygous for both traits.
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Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
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Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
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Updated: Aug 5, 2025

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
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The genetic liability to rheumatoid arthritis may decrease hepatocellular carcinoma risk in East Asian population: a

Yuzhuo Zhang1, Yudong Zhang2, Peng He1

  • 1Guangzhou Medical University, Guangzhou, 511436, Guangdong, China.

Arthritis Research & Therapy
|March 27, 2023
PubMed
Summary

Rheumatoid arthritis (RA) may surprisingly reduce hepatocellular carcinoma (HCC) risk in East Asian populations. Further research is needed to understand the underlying biological mechanisms of this unexpected association between RA and HCC.

Keywords:
Cancer riskGenome-wide association studyHepatocellular carcinomaMendelian randomizationRheumatoid arthritisSingle nucleotide polymorphisms

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Area of Science:

  • Genetics
  • Epidemiology
  • Oncology

Background:

  • Patients with rheumatoid arthritis (RA) exhibit an increased risk for certain cancers compared to the general population.
  • The specific causal relationship between rheumatoid arthritis and hepatocellular carcinoma (HCC) has not been established.

Purpose of the Study:

  • To investigate the potential causal association between rheumatoid arthritis and hepatocellular carcinoma using a bidirectional Mendelian randomization approach.
  • To determine if genetic predisposition to RA influences the risk of developing HCC in East Asian populations.

Main Methods:

  • Utilized genome-wide association study (GWAS) summary data for RA (n=19,190) and HCC (n=197,611).
  • Employed the inverse-variance weighted (IVW) method as the primary analysis, with weighted median, weighted mode, and MR-Egger analyses for robustness.
  • Validated findings using an independent RA genetic dataset (n=212,453) in East Asian populations.

Main Results:

  • Genetically predicted RA was significantly associated with a reduced risk of HCC in East Asians (OR=0.86; p=0.003).
  • Consistent results were observed with weighted median and weighted mode analyses (all p<0.05).
  • No evidence of directional pleiotropy was detected through funnel plots or MR-Egger intercepts, and results were validated with an independent RA dataset.

Conclusions:

  • Rheumatoid arthritis may be associated with a decreased risk of hepatocellular carcinoma in East Asian populations, an unexpected finding.
  • Further investigation into the potential biological mechanisms underlying the inverse relationship between RA and HCC is warranted.