Biology 1610

Chronic Pain and the

Contribution of Risk
Variants for Major
Depressive Disorder
A Summary

Ted Olsen

Introduction
In the research article titled Genetic and Environmental Risk for Chronic Pain and the
Contribution of Risk Variants for Major Depressive Disorder: A Family-Based Mixed-Model
Analysis the group of researchers sought to test the role of different genetic and environmental
factors that contributed to risk of chronic pain and its correlation with major depressive disorder.
In their hypothesis, researchers predicted that there is correlation between genetic and
environmental variables regarding the probability of individuals having chronic pain and that
major depressive disorder was affected by genetics.
Methods
Using a family-based mixed-model analyses, they examined the influence of genetics and
shared family environment to the formation of chronic pain by studying relationships between
spouse, sibling, and households. Experiments used the base of their data from the Generation
Scotland: Scottish Family Health Study a study of family and population including the Scottish
Population pulled from general practitioners. They focused on any correlation between chronic
pain and major depressive disorder and made estimations of the influence of genetic factors and
shared environments using the data of the study.
After the initial estimates of the Generation Scotland: Scottish Family Health Study they
used data from two independent genome studies to determine if chronic pain had a polygenic
architecture and if genomic risks of psychiatric conditions predicted chronic pain and if genomes
of chronic pain would predict major depressive disorder. These analyses were conducted in
Generation Scotland: Scottish Family Health Study and repeated in UK Biobank, a study of
500,000 of which 112,151 had genotyping and phenotypic data.

Results
From the two studies and the independent data researchers could make four conclusions.
Chronic pain is a moderately inheritable trait that is concordant in spouses. Chronic pain is
positively correlated with depression and shows an inclination to group within families for
genetic reasons There is polygenic risk profiles for pain, generated using the independent data
were, associated with chronic pain in both Generation Scotland: Scottish Family Health Study
and UK Biobank studies. Genomic risk of major depressive disorder is also associated with
chronic pain in both studies. The limitations the researchers noted were the possibility that
spouse correlation may be due to assortative or preferential mating and the relatively small
polygenic risk score effect sizes.
Discussion
Both genetic factors and chronic pain in a partner or spouse contribute to the risk of
chronic pain for an individual. Chronic pain is caused by an accumulation of many small genetic
effects and is associated with some of the same genetic and environmental risk factors that
determine risk of depression. Researchers confirmed their hypothesis through the analysis of the
data and could reconfirm in two additional studies that connection between Chronic pain, major
depressive disorder, and genetic and environment risks.
Conclusions
Genetic factors and chronic pain in partners or spouses contribute substantially to the risk
of chronic pain in an individual. Chronic pain does share genetic correlations with major
depressive disorder. Chronic pain also has a multiple gene architecture and is associated with
multiple gene risks of major depressive disorder.

Bibliography
McIntosh, AM, Hall LS, Zeng Y, Adams MJ, Gibson J, Wigmore E, et al. (2016) Genetic
and Environmental Risk for Chronic Pain and the Contribution of Risk Variants for Major
Depressive Disorder: A Family-Based Mixed-Model Analysis. (2015, December 21). Retrieved
November 13, 2016, PLoS Med 13(8): e10002090. Doi:10.1371/journal.pmed.1002090