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Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
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Genotype-by-environment interactions in chronic back pain.

Ivan A Kuznetsov1, Yakov A Tsepilov2, Maxim B Freidin3

  • 1Center of Life Sciences, Skolkovo Institute of Science and Technology, 30 bld.1 Bolshoy Boulevard, Moscow 121205, Russia.

The Spine Journal : Official Journal of the North American Spine Society
|April 20, 2023
PubMed
Summary

Genetic factors have minimal impact on chronic back pain (CBP) when interacting with common risk factors. Large sample sizes are needed to detect weak genotype-by-environment interactions for CBP.

Keywords:
Chronic back painGenotype-by-environment interactionsRisk factors

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Area of Science:

  • Genetics
  • Epidemiology
  • Personalized Medicine

Background:

  • Chronic back pain (CBP) is a prevalent and disabling condition with significant societal costs.
  • Understanding genotype-by-environment (GxE) interactions is key for personalized medicine approaches to CBP.
  • Few large-scale studies have systematically investigated GxE interactions for CBP, especially considering multiple risk factors.

Purpose of the Study:

  • To quantify the extent to which genetic effects on CBP are modified by known demographic and clinical risk factors.
  • To explore genotype-by-environment interactions in chronic back pain using a genome-wide approach.

Main Methods:

  • A genome-wide genotype-by-environment (GxE) interaction study was conducted using a case-control design.
  • Data from up to 331,610 UK Biobank participants (57,881 CBP cases, 273,729 controls) were analyzed.
  • Phenotypic variance explained by genotype interactions with 12 known risk factors was estimated, alongside the impact of common single-nucleotide polymorphisms on CBP in the presence of risk factors.

Main Results:

  • Genetic effects on chronic back pain (CBP) show minimal to no modification by the examined demographic and clinical risk factors.
  • The detected genotype-by-environment interactions for CBP are weak, suggesting that sample sizes in the millions would be required to reliably detect them.
  • Common genetic variations and known risk factors appear to act largely independently in predicting CBP.

Conclusions:

  • Genotype-by-environment interactions for common risk factors in chronic back pain (CBP) are either absent or too weak to influence treatment strategies.
  • Current risk estimation models for CBP can likely utilize common genetic variation and known risk factors as independent predictors.
  • The findings suggest that personalized medicine approaches for CBP may not significantly benefit from considering GxE interactions with these common factors.