Chronic pain, depression and cardiovascular disease linked through a shared genetic predisposition: Analysis of a family-based cohort and twin study

Oliver van Hecke, Lynne J Hocking, Nicola Torrance, Archie Campbell, Sandosh Padmanabhan, David J Porteous, Andrew M McIntosh, Andrea V Burri, Haruka Tanaka, Frances M K Williams, Blair H Smith

Research output: Contribution to journalArticle

12 Citations (Scopus)
5 Downloads (Pure)

Abstract

BACKGROUND: Depression and chronic pain are the two most important causes of disability (Global Burden of Disease Study 2013). They occur together more frequently than expected and both conditions have been shown to be co-morbid with cardiovascular disease. Although shared socio-demographic risk factors (e.g. gender, deprivation) might explain the co-morbidity of these three conditions, we hypothesised that these three long-term, highly prevalent conditions co-occur and may be due to shared familial risk, and/or genetic factors.

METHODS AND FINDINGS: We employed three different study designs in two independent cohorts, namely Generation Scotland and TwinsUK, having standardised, validated questionnaire data on the three traits of interest. First, we estimated the prevalence and co-occurrence of chronic pain, depression and angina among 24,024 participants of a population-based cohort of extended families (Generation Scotland: Scottish Family Health Study), adjusting for age, gender, education, smoking status, and deprivation. Secondly, we compared the odds of co-morbidity in sibling-pairs with the odds in unrelated individuals for the three conditions in the same cohort. Lastly, examination of similar traits in a sample of female twins (TwinsUK, n = 2,902), adjusting for age and BMI, allowed independent replication of the findings and exploration of the influence of additive genetic (A) factors and shared (C) and non-shared (E) environmental factors predisposing to co-occurring chronic widespread pain (CWP) and cardiovascular disease (hypertension, angina, stroke, heart attack, elevated cholesterol, angioplasty or bypass surgery). In the Generation Scotland cohort, individuals with depression were more than twice as likely to have chronic pain as those without depression (adjusted OR 2·64 [95% CI 2·34-2·97]); those with angina were four times more likely to have chronic pain (OR 4·19 [3·64-4·82]); those with depression were twice as likely to have angina (OR 2·20 [1·90-2·54]). Similar odds were obtained when the outcomes and predictors were reversed and similar effects seen among sibling pairs; depression in one sibling predicted chronic pain in the other (OR 1·34 [1·05-1·71]), angina predicted chronic pain in the other (OR 2·19 [1·63-2·95]), and depression, angina (OR 1·98 [1·49-2·65]). Individuals with chronic pain and angina showed almost four-fold greater odds of depression compared with those manifesting neither trait (OR 3·78 [2·99-4·78]); angina showed seven-fold increased odds in the presence of chronic pain and depression (OR 7·76 [6·05-9·95]) and chronic pain nine-fold in the presence of depression and angina (OR 9·43 [6·85-12·98]). In TwinsUK, the relationship between CWP and depression has been published (R = 0.34, p<0.01). Considering the CWP-cardiovascular relationship, the most suitable model to describe the observed data was a combination of A, C and E, with a small but significant genetic predisposition, shared between the two traits (2·2% [95% CI 0·06-0·23]).

CONCLUSION: We found an increased co-occurrence of chronic pain, depression and cardiovascular disease in two independent cohorts (general population-based cohort, twins cohort) suggesting a shared genetic contribution. Adjustment for known environmental influences, particularly those relating to socio-economic status (Generation Scotland: age, gender, deprivation, smoking, education; Twins UK: age,BMI) did not explain the relationship observed between chronic pain, depression and cardiovascular disease. Our findings from two independent cohorts challenge the concept of traditional disease boundaries and warrant further investigation of shared biological mechanisms.

Original languageEnglish
Article numbere0170653
Pages (from-to)1-19
Number of pages19
JournalPloS ONE
Volume12
Issue number2
DOIs
Publication statusPublished - 22 Feb 2017

Fingerprint

Twin Studies
Genetic Predisposition to Disease
Chronic Pain
cardiovascular diseases
genetic techniques and protocols
pain
Chronic Disease
Cohort Studies
Cardiovascular Diseases
Depression
Scotland
Education
Siblings
Surgery
Cholesterol
gender
Health
education
Smoking
extended families

Keywords

  • Journal Article

Cite this

van Hecke, O., Hocking, L. J., Torrance, N., Campbell, A., Padmanabhan, S., Porteous, D. J., ... Smith, B. H. (2017). Chronic pain, depression and cardiovascular disease linked through a shared genetic predisposition: Analysis of a family-based cohort and twin study. PloS ONE, 12(2), 1-19. [e0170653]. https://doi.org/10.1371/journal.pone.0170653

Chronic pain, depression and cardiovascular disease linked through a shared genetic predisposition : Analysis of a family-based cohort and twin study. / van Hecke, Oliver; Hocking, Lynne J; Torrance, Nicola; Campbell, Archie; Padmanabhan, Sandosh; Porteous, David J; McIntosh, Andrew M; Burri, Andrea V; Tanaka, Haruka; Williams, Frances M K; Smith, Blair H.

In: PloS ONE, Vol. 12, No. 2, e0170653, 22.02.2017, p. 1-19.

Research output: Contribution to journalArticle

van Hecke, O, Hocking, LJ, Torrance, N, Campbell, A, Padmanabhan, S, Porteous, DJ, McIntosh, AM, Burri, AV, Tanaka, H, Williams, FMK & Smith, BH 2017, 'Chronic pain, depression and cardiovascular disease linked through a shared genetic predisposition: Analysis of a family-based cohort and twin study', PloS ONE, vol. 12, no. 2, e0170653, pp. 1-19. https://doi.org/10.1371/journal.pone.0170653
van Hecke, Oliver ; Hocking, Lynne J ; Torrance, Nicola ; Campbell, Archie ; Padmanabhan, Sandosh ; Porteous, David J ; McIntosh, Andrew M ; Burri, Andrea V ; Tanaka, Haruka ; Williams, Frances M K ; Smith, Blair H. / Chronic pain, depression and cardiovascular disease linked through a shared genetic predisposition : Analysis of a family-based cohort and twin study. In: PloS ONE. 2017 ; Vol. 12, No. 2. pp. 1-19.
@article{deb960b3577f4c2786ff31dfd1d9e62e,
title = "Chronic pain, depression and cardiovascular disease linked through a shared genetic predisposition: Analysis of a family-based cohort and twin study",
abstract = "BACKGROUND: Depression and chronic pain are the two most important causes of disability (Global Burden of Disease Study 2013). They occur together more frequently than expected and both conditions have been shown to be co-morbid with cardiovascular disease. Although shared socio-demographic risk factors (e.g. gender, deprivation) might explain the co-morbidity of these three conditions, we hypothesised that these three long-term, highly prevalent conditions co-occur and may be due to shared familial risk, and/or genetic factors.METHODS AND FINDINGS: We employed three different study designs in two independent cohorts, namely Generation Scotland and TwinsUK, having standardised, validated questionnaire data on the three traits of interest. First, we estimated the prevalence and co-occurrence of chronic pain, depression and angina among 24,024 participants of a population-based cohort of extended families (Generation Scotland: Scottish Family Health Study), adjusting for age, gender, education, smoking status, and deprivation. Secondly, we compared the odds of co-morbidity in sibling-pairs with the odds in unrelated individuals for the three conditions in the same cohort. Lastly, examination of similar traits in a sample of female twins (TwinsUK, n = 2,902), adjusting for age and BMI, allowed independent replication of the findings and exploration of the influence of additive genetic (A) factors and shared (C) and non-shared (E) environmental factors predisposing to co-occurring chronic widespread pain (CWP) and cardiovascular disease (hypertension, angina, stroke, heart attack, elevated cholesterol, angioplasty or bypass surgery). In the Generation Scotland cohort, individuals with depression were more than twice as likely to have chronic pain as those without depression (adjusted OR 2·64 [95{\%} CI 2·34-2·97]); those with angina were four times more likely to have chronic pain (OR 4·19 [3·64-4·82]); those with depression were twice as likely to have angina (OR 2·20 [1·90-2·54]). Similar odds were obtained when the outcomes and predictors were reversed and similar effects seen among sibling pairs; depression in one sibling predicted chronic pain in the other (OR 1·34 [1·05-1·71]), angina predicted chronic pain in the other (OR 2·19 [1·63-2·95]), and depression, angina (OR 1·98 [1·49-2·65]). Individuals with chronic pain and angina showed almost four-fold greater odds of depression compared with those manifesting neither trait (OR 3·78 [2·99-4·78]); angina showed seven-fold increased odds in the presence of chronic pain and depression (OR 7·76 [6·05-9·95]) and chronic pain nine-fold in the presence of depression and angina (OR 9·43 [6·85-12·98]). In TwinsUK, the relationship between CWP and depression has been published (R = 0.34, p<0.01). Considering the CWP-cardiovascular relationship, the most suitable model to describe the observed data was a combination of A, C and E, with a small but significant genetic predisposition, shared between the two traits (2·2{\%} [95{\%} CI 0·06-0·23]).CONCLUSION: We found an increased co-occurrence of chronic pain, depression and cardiovascular disease in two independent cohorts (general population-based cohort, twins cohort) suggesting a shared genetic contribution. Adjustment for known environmental influences, particularly those relating to socio-economic status (Generation Scotland: age, gender, deprivation, smoking, education; Twins UK: age,BMI) did not explain the relationship observed between chronic pain, depression and cardiovascular disease. Our findings from two independent cohorts challenge the concept of traditional disease boundaries and warrant further investigation of shared biological mechanisms.",
keywords = "Journal Article",
author = "{van Hecke}, Oliver and Hocking, {Lynne J} and Nicola Torrance and Archie Campbell and Sandosh Padmanabhan and Porteous, {David J} and McIntosh, {Andrew M} and Burri, {Andrea V} and Haruka Tanaka and Williams, {Frances M K} and Smith, {Blair H}",
note = "Funding: FMKW is supported by Arthritis Research UK grant 20682 and by EU FP7 project Pain-omics. AB reports an Ambizione personal career fellowship by the Swiss National Science Foundation and a project grant from the Swisslife Jubil{\"a}umsstiftung. Generation Scotland (www.generationscotland.org) has received core funding from the Chief Scientist Office of the Scottish Government Health Directorates CZD/16/6 and the Scottish Funding Council HR03006. The sponsor of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report, or the decision to submit for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. TwinsUK (www.twinsuk.ac.uk): the study was funded by the Wellcome Trust; European Community’s Seventh Framework Programme (FP7/2007-2013). The study also receives support from the National Institute for Health Research (NIHR)- funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We are grateful to the families who took part in GS:SFHS, the GPs and Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team, which includes academic researchers, clinic staff, laboratory technicians, clerical workers, statisticians and research managers. FMKW is supported by Arthritis Research UK grant 20682 and by EU FP7 project Painomics. AB reports an Ambizione personal career fellowship by the Swiss National Science Foundation and a project grant from the Swisslife Jubilaumsstiftung. https://figshare.com/articles/Chronic_pain_depression_and_cardiovascular_disease_linked_through_a_shared_genetic_predisposition_Analysis_of_a_family-based_cohort_and_twin_study/4681744",
year = "2017",
month = "2",
day = "22",
doi = "10.1371/journal.pone.0170653",
language = "English",
volume = "12",
pages = "1--19",
journal = "PloS ONE",
issn = "1932-6203",
publisher = "PUBLIC LIBRARY SCIENCE",
number = "2",

}

TY - JOUR

T1 - Chronic pain, depression and cardiovascular disease linked through a shared genetic predisposition

T2 - Analysis of a family-based cohort and twin study

AU - van Hecke, Oliver

AU - Hocking, Lynne J

AU - Torrance, Nicola

AU - Campbell, Archie

AU - Padmanabhan, Sandosh

AU - Porteous, David J

AU - McIntosh, Andrew M

AU - Burri, Andrea V

AU - Tanaka, Haruka

AU - Williams, Frances M K

AU - Smith, Blair H

N1 - Funding: FMKW is supported by Arthritis Research UK grant 20682 and by EU FP7 project Pain-omics. AB reports an Ambizione personal career fellowship by the Swiss National Science Foundation and a project grant from the Swisslife Jubiläumsstiftung. Generation Scotland (www.generationscotland.org) has received core funding from the Chief Scientist Office of the Scottish Government Health Directorates CZD/16/6 and the Scottish Funding Council HR03006. The sponsor of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report, or the decision to submit for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. TwinsUK (www.twinsuk.ac.uk): the study was funded by the Wellcome Trust; European Community’s Seventh Framework Programme (FP7/2007-2013). The study also receives support from the National Institute for Health Research (NIHR)- funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We are grateful to the families who took part in GS:SFHS, the GPs and Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team, which includes academic researchers, clinic staff, laboratory technicians, clerical workers, statisticians and research managers. FMKW is supported by Arthritis Research UK grant 20682 and by EU FP7 project Painomics. AB reports an Ambizione personal career fellowship by the Swiss National Science Foundation and a project grant from the Swisslife Jubilaumsstiftung. https://figshare.com/articles/Chronic_pain_depression_and_cardiovascular_disease_linked_through_a_shared_genetic_predisposition_Analysis_of_a_family-based_cohort_and_twin_study/4681744

PY - 2017/2/22

Y1 - 2017/2/22

N2 - BACKGROUND: Depression and chronic pain are the two most important causes of disability (Global Burden of Disease Study 2013). They occur together more frequently than expected and both conditions have been shown to be co-morbid with cardiovascular disease. Although shared socio-demographic risk factors (e.g. gender, deprivation) might explain the co-morbidity of these three conditions, we hypothesised that these three long-term, highly prevalent conditions co-occur and may be due to shared familial risk, and/or genetic factors.METHODS AND FINDINGS: We employed three different study designs in two independent cohorts, namely Generation Scotland and TwinsUK, having standardised, validated questionnaire data on the three traits of interest. First, we estimated the prevalence and co-occurrence of chronic pain, depression and angina among 24,024 participants of a population-based cohort of extended families (Generation Scotland: Scottish Family Health Study), adjusting for age, gender, education, smoking status, and deprivation. Secondly, we compared the odds of co-morbidity in sibling-pairs with the odds in unrelated individuals for the three conditions in the same cohort. Lastly, examination of similar traits in a sample of female twins (TwinsUK, n = 2,902), adjusting for age and BMI, allowed independent replication of the findings and exploration of the influence of additive genetic (A) factors and shared (C) and non-shared (E) environmental factors predisposing to co-occurring chronic widespread pain (CWP) and cardiovascular disease (hypertension, angina, stroke, heart attack, elevated cholesterol, angioplasty or bypass surgery). In the Generation Scotland cohort, individuals with depression were more than twice as likely to have chronic pain as those without depression (adjusted OR 2·64 [95% CI 2·34-2·97]); those with angina were four times more likely to have chronic pain (OR 4·19 [3·64-4·82]); those with depression were twice as likely to have angina (OR 2·20 [1·90-2·54]). Similar odds were obtained when the outcomes and predictors were reversed and similar effects seen among sibling pairs; depression in one sibling predicted chronic pain in the other (OR 1·34 [1·05-1·71]), angina predicted chronic pain in the other (OR 2·19 [1·63-2·95]), and depression, angina (OR 1·98 [1·49-2·65]). Individuals with chronic pain and angina showed almost four-fold greater odds of depression compared with those manifesting neither trait (OR 3·78 [2·99-4·78]); angina showed seven-fold increased odds in the presence of chronic pain and depression (OR 7·76 [6·05-9·95]) and chronic pain nine-fold in the presence of depression and angina (OR 9·43 [6·85-12·98]). In TwinsUK, the relationship between CWP and depression has been published (R = 0.34, p<0.01). Considering the CWP-cardiovascular relationship, the most suitable model to describe the observed data was a combination of A, C and E, with a small but significant genetic predisposition, shared between the two traits (2·2% [95% CI 0·06-0·23]).CONCLUSION: We found an increased co-occurrence of chronic pain, depression and cardiovascular disease in two independent cohorts (general population-based cohort, twins cohort) suggesting a shared genetic contribution. Adjustment for known environmental influences, particularly those relating to socio-economic status (Generation Scotland: age, gender, deprivation, smoking, education; Twins UK: age,BMI) did not explain the relationship observed between chronic pain, depression and cardiovascular disease. Our findings from two independent cohorts challenge the concept of traditional disease boundaries and warrant further investigation of shared biological mechanisms.

AB - BACKGROUND: Depression and chronic pain are the two most important causes of disability (Global Burden of Disease Study 2013). They occur together more frequently than expected and both conditions have been shown to be co-morbid with cardiovascular disease. Although shared socio-demographic risk factors (e.g. gender, deprivation) might explain the co-morbidity of these three conditions, we hypothesised that these three long-term, highly prevalent conditions co-occur and may be due to shared familial risk, and/or genetic factors.METHODS AND FINDINGS: We employed three different study designs in two independent cohorts, namely Generation Scotland and TwinsUK, having standardised, validated questionnaire data on the three traits of interest. First, we estimated the prevalence and co-occurrence of chronic pain, depression and angina among 24,024 participants of a population-based cohort of extended families (Generation Scotland: Scottish Family Health Study), adjusting for age, gender, education, smoking status, and deprivation. Secondly, we compared the odds of co-morbidity in sibling-pairs with the odds in unrelated individuals for the three conditions in the same cohort. Lastly, examination of similar traits in a sample of female twins (TwinsUK, n = 2,902), adjusting for age and BMI, allowed independent replication of the findings and exploration of the influence of additive genetic (A) factors and shared (C) and non-shared (E) environmental factors predisposing to co-occurring chronic widespread pain (CWP) and cardiovascular disease (hypertension, angina, stroke, heart attack, elevated cholesterol, angioplasty or bypass surgery). In the Generation Scotland cohort, individuals with depression were more than twice as likely to have chronic pain as those without depression (adjusted OR 2·64 [95% CI 2·34-2·97]); those with angina were four times more likely to have chronic pain (OR 4·19 [3·64-4·82]); those with depression were twice as likely to have angina (OR 2·20 [1·90-2·54]). Similar odds were obtained when the outcomes and predictors were reversed and similar effects seen among sibling pairs; depression in one sibling predicted chronic pain in the other (OR 1·34 [1·05-1·71]), angina predicted chronic pain in the other (OR 2·19 [1·63-2·95]), and depression, angina (OR 1·98 [1·49-2·65]). Individuals with chronic pain and angina showed almost four-fold greater odds of depression compared with those manifesting neither trait (OR 3·78 [2·99-4·78]); angina showed seven-fold increased odds in the presence of chronic pain and depression (OR 7·76 [6·05-9·95]) and chronic pain nine-fold in the presence of depression and angina (OR 9·43 [6·85-12·98]). In TwinsUK, the relationship between CWP and depression has been published (R = 0.34, p<0.01). Considering the CWP-cardiovascular relationship, the most suitable model to describe the observed data was a combination of A, C and E, with a small but significant genetic predisposition, shared between the two traits (2·2% [95% CI 0·06-0·23]).CONCLUSION: We found an increased co-occurrence of chronic pain, depression and cardiovascular disease in two independent cohorts (general population-based cohort, twins cohort) suggesting a shared genetic contribution. Adjustment for known environmental influences, particularly those relating to socio-economic status (Generation Scotland: age, gender, deprivation, smoking, education; Twins UK: age,BMI) did not explain the relationship observed between chronic pain, depression and cardiovascular disease. Our findings from two independent cohorts challenge the concept of traditional disease boundaries and warrant further investigation of shared biological mechanisms.

KW - Journal Article

U2 - 10.1371/journal.pone.0170653

DO - 10.1371/journal.pone.0170653

M3 - Article

C2 - 28225781

VL - 12

SP - 1

EP - 19

JO - PloS ONE

JF - PloS ONE

SN - 1932-6203

IS - 2

M1 - e0170653

ER -