Genetic, lifestyle and environmental risk factors for chronic pain revealed through GWAS

Lundberg, Mischa; Campos, Adrián I.; Farrell, Scott F.; Geng, Wang; Sterling, Michele; Rentería, Miguel E.; Ngo, Trung Thanh; Cuéllar-Partida, Gabriel

doi:10.1101/2020.05.26.115568

Cited by 5 publications

(7 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Table 3) -this is comparable to genetic correlation values seen between chronic pain traits and MDD [149]. Genetic correlation of 0.26 between migraine and ADHD has also been described [297], and Lundberg et al [298] also note a "positive" genetic correlation value between ADHD and chronic pain (Fig. 1).…”

Section: Genetic Correlationsupporting

confidence: 78%

Chronic Pain and Psychiatric Conditions

Johnston¹,

Huckins²

2022

Complex Psychiatry

View full text Add to dashboard Cite

Chronic pain is a common condition with high socioeconomic and public health burden. A wide range of psychiatric conditions are often comorbid with chronic pain and chronic pain conditions, negatively impacting successful treatment of either condition. The psychiatric condition receiving most attention in the past with regards to chronic pain comorbidity has been major depressive disorder, despite the fact that many other psychiatric conditions also demonstrate epidemiological and genetic overlap with chronic pain. Further understanding potential mechanisms involved in psychiatric and chronic pain comorbidity could lead to new treatment strategies both for each type of disorder in isolation, and in scenarios of comorbidity. This article provides an overview of relationships between DSM-5 psychiatric diagnoses and chronic pain, with particular focus on PTSD, ADHD and BPD, disorders which are less commonly studied in conjunction with chronic pain. We also discuss potential mechanisms that may drive comorbidity, and present new findings on the genetic overlap of chronic pain and ADHD, and chronic pain and BPD.

show abstract

Section: Genetic Correlationsupporting

confidence: 78%

Chronic Pain and Psychiatric Conditions

Johnston¹,

Huckins²

2022

Complex Psychiatry

View full text Add to dashboard Cite

show abstract

“…Lundberg et al. (2020) found a genetic correlation ( r g = 0.42) between smoking and wide‐spread chronic pain in a genome‐wide association study. These results suggest shared risk alleles underlie the pain‐smoking association.…”

Section: Discussionmentioning

confidence: 99%

“…Although the genetic correlation we detected may be due to a mixture of genetic and correlated shared environmental effects that we are unable to discriminate, our estimate (r g = 0.51) is similar to a recent estimate from a genome-based method. Lundberg et al (2020) found a genetic correlation (r g = 0.42) between smoking and wide-spread chronic pain in a genome-wide association study. These results suggest shared risk alleles underlie the pain-smoking association.…”

Section: Significant Shared Genetic Influences On Smoking and Painmentioning

confidence: 94%

“…gene-environment correlations pain and smoking (in which case they might captured by the genetic correlation for pain and smoking). Lifestyle habits such as nutrition, sleep, physical activity, and obesity, have been linked to chronic pain and smoking, both phenotypically and genetically (Lundberg et al, 2020;Mills et al, 2019). A gene-environment interaction is also plausible, where genetic risk depends on an individual's environment (Purcell, 2002).…”

Section: Significant Shared Genetic Influences On Smoking and Painmentioning

confidence: 99%

See 1 more Smart Citation

Familial effects account for association between chronic pain and past month smoking

Rader,

Reineberg,

Petre

et al. 2024

European Journal of Pain

View full text Add to dashboard Cite

BackgroundSmoking is associated with chronic pain, but it is not established whether smoking causes pain or if the link is due to familial effects. One proposed mechanism is that smoking strengthens maladaptive cortico‐striatal connectivity, which contributes to pain chronification. We leveraged a twin design to assess direct effects of smoking on pain controlling for familial confounds, and whether cortico‐striatal connectivity mediates this association.MethodsIn a population‐based sample of 692 twins (age = 28.83 years), we assessed past‐month smoking frequency (n = 132 used in the past month), presence and severity of a current pain episode (n = 179 yes), and resting‐state functional connectivity of the nucleus accumbens and medial prefrontal cortex (NAc‐mPFC).ResultsSmoking was significantly associated with pain, but the association was not significantly mediated by NAc‐mPFC connectivity. In a co‐twin control model, smoking predicted which families had more pain but could not distinguish pain between family members. Pain risk was 43% due to additive genetic (A) and 57% due to non‐shared environmental (E) influences. Past‐month smoking frequency was 71% genetic and 29% non‐shared environmental. Smoking and pain significantly correlated phenotypically (r = 0.21, p = 0.001) and genetically (rg = 0.51, p < 0.001), but not environmentally (re = −0.18, p = 0.339).ConclusionsPain and smoking are associated; however, the association appears to reflect shared familial risk factors, such as genetic risk, rather than being causal in nature. The connectivity strength of the reward pathway was not related to concurrent pain and smoking in this sample.SignificanceSmoking does not appear to directly cause chronic pain; rather, there may be shared biopsychosocial risk factors, including genetic influences, that explain their association. These findings can be integrated into future research to identify shared biological pathways of both chronic pain and smoking behaviours as a way to conceptualize pain chronification.

show abstract

“…Previous clinical & epidemiological studies have found a range of psychiatric (e.g., stress, depression, trauma, anxiety 26,27 ), lifestyle (e.g., smoking, 28,29 sedentary behaviour 30,31 ) and socioeconomic factors (e.g., income & education levels 32,33 ) associated with an increased risk of chronic pain, while medical conditions such as obesity 34 & cardiovascular diseases 35,36 are also common comorbidities. 37 Large-scale GWAS have identified specific genetic loci in chronic pain conditions (e.g., back, 12,19 neck/shoulder, 15 knee pain 9 & widespread pain 14,20 ) and demonstrated shared genetic bases with biopsychosocial traits (e.g., depression, 19,20,27 post-traumatic stress disorder, 20 anorexia nervosa, 38 asthma, 20 brain morphology, 18 poor sleep, 8,19,39 obesity, 5 low educational attainment 19,40 & smoking 19,40 ). However, the nature of causal relationships between common chronic pain conditions and such multidimensional factors remains to be comprehensively examined.…”

Section: Introductionmentioning

confidence: 99%

A shared genetic signature for common chronic pain conditions and its impact on biopsychosocial traits

Farrell

Kho

Campos

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Background: The multifactorial heterogenous nature of chronic pain with its multiple comorbidities presents a formidable challenge in disentangling the aetiology underlying patient symptoms. Methods: Here, we performed genome-wide association studies (GWAS) of eight types of regional chronic pain using UK Biobank data (N=4,037-79,089 cases; N=239,125 controls), followed by bivariate linkage disequilibrium-score regression and latent causal variable analyses to determine (respectively) their genetic correlations and genetic causal proportion (GCP) parameters with 1,492 other complex traits. Findings: We report evidence of a shared genetic signature in common regional chronic pain types, with their genetic correlations and causal directions being broadly consistent across a wide array of biopsychosocial traits. Furthermore, we identified 5,942 significant genetic correlations, of which 570 trait pairs showed evidence of a likely causal association (|GCP| > 0.6; 5% false discovery rate), including 488 traits contributing to chronic pain while 82 were affected by pain. A range of somatic pathologies (e.g., musculoskeletal, visceral), psychiatric factors (e.g., depression, trauma, anxiety, mania, bipolar disorder), socioeconomic factors (e.g., occupation) and other medical comorbidities (e.g., cardiovascular disease) contributed to an increased risk of regional chronic pain. Conversely, each chronic pain type contributed to various other traits such as increased medication use (e.g., analgesics) and risk of ischaemic heart disease and depression. Interpretation: Findings of this data-driven study, through comprehensive analysis of a vast range of biopsychosocial factors, are indicative of a common genetic signature underlying eight regional chronic pain types. We identify a broad range of traits with genetic causal effects upon chronic pain, which may inform development of novel diagnostic and therapeutic strategies, as well as provide convergent support for various existing approaches.

show abstract

Genetic, lifestyle and environmental risk factors for chronic pain revealed through GWAS

Cited by 5 publications

References 82 publications

Chronic Pain and Psychiatric Conditions

Chronic Pain and Psychiatric Conditions

Familial effects account for association between chronic pain and past month smoking

A shared genetic signature for common chronic pain conditions and its impact on biopsychosocial traits

Contact Info

Product

Resources

About