scholarly journals Identification of novel common variants associated with chronic pain using conditional false discovery rate analysis with major depressive disorder and assessment of pleiotropic effects of LRFN5

2018 ◽  
Author(s):  
Keira J.A. Johnston ◽  
Mark J. Adams ◽  
Barbara I. Nicholl ◽  
Joey Ward ◽  
Rona J Strawbridge ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
False Discovery Rate ◽  
Complex Traits ◽  
Pleiotropic Effects ◽  
Chromosome 1 ◽  
Chromosome 14 ◽  
Major Depressive ◽  
False Discovery

AbstractChronic pain is highly prevalent worldwide, with a significant socioeconomic burden, and also contributes to excess mortality. Chronic pain is a complex trait that is moderately heritable and genetically, as well as phenotypically, correlated with major depressive disorder (MDD). Use of the Conditional False Discovery Rate (cFDR) approach, which leverages pleiotropy identified from existing GWAS outputs, has been successful in discovering novel associated variants in related phenotypes. Here, genome-wide association study outputs for both von Korff chronic pain grade as a quasi-quantitative trait and for MDD were used to identify variants meeting a cFDR threshold for each outcome phenotype separately, as well as a conjunctional cFDR (ccFDR) threshold for both phenotypes together. Using a moderately conservative threshold, we identified a total of 11 novel single nucleotide polymorphisms (SNPs), six of which were associated with chronic pain grade and nine of which were associated with MDD. Four SNPs on chromosome 14 were associated with both chronic pain grade and MDD. SNPs associated only with chronic pain grade were located within SLC16A7 on chromosome 12. SNPs associated only with MDD were located either in a gene-dense region on chromosome 1 harbouring LINC01360, LRRIQ3, FPGT and FPGT-TNNI3K, or within/close to LRFN5 on chromosome 14. The SNPs associated with both outcomes were also located within LRFN5. Several of the SNPs on chromosomes 1 and 14 were identified as being associated with expression levels of nearby genes in the brain and central nervous system. Overall, using the cFDR approach, we identified several novel genetic loci associated with chronic pain and we describe likely pleiotropic effects of a recently identified MDD locus on chronic pain.Author SummaryGenetic variants explaining variation in complex traits can often be associated with more than one trait at once (‘pleiotropy’). Taking account of this pleiotropy in genetic studies can increase power to find sites in the genome harbouring trait-associated variants. In this study we used the suspected underlying pleiotropy between chronic pain and major depressive disorder to discover novel variants associated with chronic pain, and to investigate genetic variation that may be shared between the two disorders.

scholarly journals Identification of novel common variants associated with chronic pain using conditional false discovery rate analysis with major depressive disorder and assessment of pleiotropic effects of LRFN5

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Keira J. A. Johnston ◽  
Mark J. Adams ◽  
Barbara I. Nicholl ◽  
Joey Ward ◽  
Rona J. Strawbridge ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
False Discovery Rate ◽  
Genome Wide Association Study ◽  
Pleiotropic Effects ◽  
Chromosome 1 ◽  
Chromosome 14 ◽  
Major Depressive ◽  
False Discovery

AbstractChronic pain is a complex trait that is moderately heritable and genetically, as well as phenotypically, correlated with major depressive disorder (MDD). Use of the conditional false discovery rate (cFDR) approach, which leverages pleiotropy identified from existing GWAS outputs, has been successful in discovering novel associated variants in related phenotypes. Here, genome-wide association study outputs for both von Korff chronic pain grade and for MDD were used to identify variants meeting a cFDR threshold for each outcome phenotype separately, as well as a conjunctional cFDR (ccFDR) threshold for both phenotypes together. Using a moderately conservative threshold, we identified a total of 11 novel single nucleotide polymorphisms (SNPs), six of which were associated with chronic pain grade and nine of which were associated with MDD. Four SNPs on chromosome 14 were associated with both chronic pain grade and MDD. SNPs associated only with chronic pain grade were located within SLC16A7 on chromosome 12. SNPs associated only with MDD were located either in a gene-dense region on chromosome 1 harbouring LINC01360, LRRIQ3, FPGT and FPGT-TNNI3K, or within/close to LRFN5 on chromosome 14. The SNPs associated with both outcomes were also located within LRFN5. Several of the SNPs on chromosomes 1 and 14 were identified as being associated with expression levels of nearby genes in the brain and central nervous system. Overall, using the cFDR approach, we identified several novel genetic loci associated with chronic pain and we describe likely pleiotropic effects of a recently identified MDD locus on chronic pain.

scholarly journals The association between alexithymia and two dimensions of major depressive disorder: cognitive and somatic-affective

2020 ◽  
Vol 57 (1) ◽  
pp. 39-52
Author(s):  
Maja Vilibić ◽  
Anita Dostal ◽  
Dalibor Karlović
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
False Discovery Rate ◽  
Target Population ◽  
Two Dimensions ◽  
University Hospital ◽  
Major Depressive ◽  
Cross Sectional ◽  
Cognitive Dimension ◽  
False Discovery

Aim: To explore the association between alexithymia and two dimensions of major depressive disorder (MDD): cognitive and somatic-affective. Patients and methods. Unicentric, cross-sectional study included consecutive sample of 63 patients at the Department of Psychiatry (DoP), Sestre Milosrdnice University Hospital Centre, Zagreb, Croatia. Target population included outpatients with diagnosed MDD (F32 and F33, according to ICD-10). Inclusion criteria were: confirmed MDD diagnosis, age between 18 and 65 years, both genders, outpatient treatment at the DoP. The main outcome was the association between alexithymia, measured by total score on 20-item Toronto-Alexithymia scale (TAS-20), with two dimensions of MDD, cognitive and somatic-affective, measured by Beck Depression Inventory-II (BDI-II). Results: Both dimensions of BDI-II and the total severity of MDD symptoms were statistically significantly, although low, associated with alexithymia, and the differences between these two correlations were not (statistically) significant. However, in the multivariable model, the cognitive dimension (b = 0.64; β = 0.48; p = 0.002; statistically significant at the false discovery rate of 0.05) was primarily associated with alexithymia, and the somatic-affective was not, after all cognitive aspects were controlled for (b = -0.19; β = 0-0.14; p = 0.491; not statistically significant, with the false discovery rate of 0.05). Conclusion: Alexithymia is primarily associated with a pure cognitive dimension of MDD after somatic-affective elements are excluded. Somatic-affective dimension of MDD is not associated with alexithymia after the cognitive elements were controlled for. Both dimensions, as well as the overall severity of MDD, are associated with alexithymia, but this association is relatively low.

scholarly journals Polygenic interactions with environmental adversity in the aetiology of major depressive disorder

2015 ◽  
Vol 46 (4) ◽  
pp. 759-770 ◽  
Author(s):  
N. Mullins ◽  
R. A. Power ◽  
H. L. Fisher ◽  
K. B. Hanscombe ◽  
J. Euesden ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Environmental Risk ◽  
Complex Traits ◽  
Risk Scores ◽  
Environment Interaction ◽  
Inverse Association ◽  
Major Depressive ◽  
Polygenic Risk ◽  
Gene Environment

BackgroundMajor depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD.MethodThe RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them.ResultsPRS significantly predicted depression, explaining 1.1% of variance in phenotype (p= 1.9 × 10−6). SLEs and CT were also associated with MDD status (p= 2.19 × 10−4andp= 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p= 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples.ConclusionsCT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.

scholarly journals SNP and Haplotype Regional Heritability Mapping (SNHap-RHM): joint mapping of common and rare variation affecting complex traits

2021 ◽  
Author(s):  
Richard F Oppong ◽  
Pau Navarro ◽  
Chris S Haley ◽  
Sara Knott
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Complex Traits ◽  
Health Study ◽  
P Value ◽  
Major Depressive ◽  
Genome Wide ◽  
A Genome ◽  
Joint Mapping ◽  
Genomic Regions

We describe a genome-wide analytical approach, SNP and Haplotype Regional Heritability Mapping (SNHap-RHM), that provides regional estimates of the heritability across locally defined regions in the genome. This approach utilises relationship matrices that are based on sharing of SNP and haplotype alleles at local haplotype blocks delimited by recombination boundaries in the genome. We implemented the approach on simulated data and show that the haplotype-based regional GRMs capture variation that is complementary to that captured by SNP-based regional GRMs, and thus justifying the fitting of the two GRMs jointly in a single analysis (SNHap-RHM). SNHap-RHM captures regions in the genome contributing to the phenotypic variation that existing genome-wide analysis methods may fail to capture. We further demonstrate that there are real benefits to be gained from this approach by applying it to real data from about 20,000 individuals from the Generation Scotland: Scottish Family Health Study. We analysed height and major depressive disorder (MDD). We identified seven genomic regions that are genome-wide significant for height, and three regions significant at a suggestive threshold (p-value <1x10^(-5) ) for MDD. These significant regions have genes mapped to within 400kb of them. The genes mapped for height have been reported to be associated with height in humans, whiles those mapped for MDD have been reported to be associated with major depressive disorder and other psychiatry phenotypes. The results show that SNHap-RHM presents an exciting new opportunity to analyse complex traits by allowing the joint mapping of novel genomic regions tagged by either SNPs or haplotypes, potentially leading to the recovery of some of the "missing" heritability.

Alternative diagnostic criteria for major depressive disorder in patients with chronic pain

Pain ◽  
2001 ◽  
Vol 91 (3) ◽  
pp. 227-234 ◽  
Author(s):  
Keith G. Wilson ◽  
Samuel F. Mikail ◽  
Joyce L. DʼEon ◽  
Joanne E. Minns
Keyword(s):  
Chronic Pain ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Diagnostic Criteria ◽  
Major Depressive

scholarly journals Major Depressive Disorder and Sleep Disturbance in Patients with Chronic Pain

2014 ◽  
Vol 19 (1) ◽  
pp. 35-41 ◽  
Author(s):  
Patricia C Emery ◽  
Keith G Wilson ◽  
John Kowal
Keyword(s):  
Chronic Pain ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Sleep Hygiene ◽  
Dysfunctional Beliefs ◽  
Major Depressive ◽  
Hygiene Practices ◽  
Chronic Pain Patients ◽  
Pain Patients ◽  
Presleep Arousal

BACKGROUND: Disturbed sleep is a common problem in both chronic pain and major depressive disorder (MDD). Moreover, many patients with chronic pain are depressed.OBJECTIVES: To examine the effects of depression on the sleep behaviour of chronic pain patients by comparing patients who did or did not meet diagnostic criteria for MDD.METHODS: A total of 60 patients with chronic musculoskeletal pain underwent structured diagnostic interviews for MDD and insomnia, and completed questionnaires assessing pain severity, disability, sleep quality, beliefs and attitudes about sleep, and sleep hygiene. For four consecutive days, they also completed a sleep diary, and reported on sleep hygiene practices and presleep arousal.RESULTS: Thirty-three patients (55%) met diagnostic criteria for MDD, most of whom (n=32 [97%]) also fulfilled criteria for insomnia disorder. Insomnia was also common among patients without MDD (21 of 27 [78%]). Participants with MDD had higher self-reports of pain, disability, dysfunctional beliefs about sleep, and, on a prospective basis, greater presleep arousal and poorer sleep hygiene. However, diary assessments of specific sleep parameters (eg, sleep onset latency, total sleep time, sleep efficiency) did not differ between the groups.DISCUSSION: Chronic pain patients with comorbid MDD exhibited more dysfunctional beliefs about sleep, poorer sleep hygiene practices and greater presleep arousal; however, diary-recorded sleep characteristics may not differ from those of patients without MDD. Chronic pain itself may disturb sleep so extensively that MDD introduces little additive effect.CONCLUSION: MDD in chronic pain may be related to the cognitive and behavioural aspects of insomnia, rather than to an incremental disturbance in the initiation or maintenance of sleep.

scholarly journals Diagnosing Depression in Chronic Pain Patients: DSM-IV Major Depressive Disorder vs. Beck Depression Inventory (BDI)

PLoS ONE ◽  
2016 ◽  
Vol 11 (3) ◽  
pp. e0151982 ◽  
Author(s):  
Peter Knaster ◽  
Ann-Mari Estlander ◽  
Hasse Karlsson ◽  
Jaakko Kaprio ◽  
Eija Kalso
Keyword(s):  
Chronic Pain ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Beck Depression Inventory ◽  
Major Depressive ◽  
Chronic Pain Patients ◽  
Dsm Iv ◽  
Pain Patients
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