Common genomic pathways between endometriosis and fibromyalgia

Thesis

Endometriosis and fibromyalgia are often comorbid conditions and are part of a larger group of conditions known as chronic overlapping pain conditions which share many symptoms and pain mechanisms. Endometriosis is a secondary chronic pain condition, where there is peripheral pathology underlying the pain, whereas fibromyalgia is a primary chronic pain condition, with no known underlying pathology.

The aim of my thesis is to uncover the shared genetic basis of fibromyalgia and endometriosis. To investigate current knowledge of the genetic overlap between primary and secondary chronic pain conditions, I conducted a systematic review. I identified NGF, ASTN2 and LRP1 as possible pain susceptibility genes with pleiotropic effects in both primary and secondary pain conditions. To address the knowledge gap in the genetics of fibromyalgia, I conducted a genome-wide association study (GWAS) in UK Biobank, which illustrated that different case definitions show genetic heterogeneity. To boost power of discovery, I meta-analysed UK Biobank ICD-based fibromyalgia GWAS with a fibromyalgia GWAS from FinnGen. One lead SNP was identified, rs34323745, which nearly reached genome-wide significance (p = 7.269 x 10-8). To study the shared genetic basis of endometriosis and fibromyalgia, I conducted a multi-trait association study using the meta-analysis of fibromyalgia from UK Biobank and FinnGen and the largest published meta-analysis of endometriosis to date (Rahmioglu et al., 2023). I identified two genome-wide significant hits, rs17082358 on chromosome 2 in the SYNE1 locus (p = 1.49 x 10-11) and rs13432756 on chromosome 6 in the GREB1 locus (p = 6.39 x 10-9). Both loci have previously been associated with endometriosis. GREB1 was previously associated with fibromyalgia, but not in a large genetic study. Future studies are needed to replicate these findings and to better understand the biology of GREB1 and SYNE1 as shared genes in fibromyalgia and endometriosis.

Authors: Lucinescu, I-W

• DOI: 10.5287/ora-2n12rojny
• Type of award: MSc by Research
• Level of award: Masters
• Awarding institution: University of Oxford
• Language: English
• Keywords: genomics; endometriosis; bioinformatics; fibromyalgia; genome-wide association study
• Subjects: Bioinformatics; Fibromyalgia; Common diseases; Endometriosis; Human genetics--Variation; Genomics