Genome-Wide Association Analysis Identified ANXA1 Associated with Shoulder Impingement Syndrome in UK Biobank Samples

Abstract

Shoulder impingement syndrome (SIS) is a common shoulder disorder with unclear genetic mechanism. In this study, Genome-wide Association Study (GWAS) was conducted to identify the candidate loci associated with SIS by using the UK Biobank samples (including 3,626 SIS patients and 3,626 control subjects). Based on the GWAS results, gene sets enrichment analysis was further performed to detect the candidate gene ontology and pathways associated with SIS. We identified multiple risk loci associated with SIS, such as rs750968 (P = 4.82 × 10−8), rs754832 (P = 4.83 × 10−8) and rs1873119 (P = 6.39 × 10−8) of ANXA1 gene. Some candidate pathways has been identified related to SIS, such as "ZHOU_INFLAMMATORY_RESPONSE_FIMA_DN" (P = 0.012), "MANALO_HYPOXIA_UP" (P = 5.00× 10−5) and "BECKER_TAMOXIFEN_RESISTANCE_DN" (P = 1.00× 10−4). Our results provided novel clues for understanding the genetic mechanism of SIS.

Omics approaches to discover pathophysiological pathways contributing to human pain

“…This may be one reason why post-GWAS functional analyses for pain phenotypes identify more robust evidence for brainexpressed genes among top associated SNPs, 6,20,33,35,49 but less evidence for immune cell-specific SNPs. 6,10,35,70 The enrichment for brain-expressed genes in the GWAS results may be a reflection of the linear dose-dependent and time-dependent relationship between neuronal processes and chronic pain development, in contrast to the curvilinear features of immune cell processes. 84 Panels show intraepidermal innervation (purple) in control human subjects (left) and patients with fibromyalgia (right).…”

“… 63 Finally, immune system genes were found to contribute to back pain, 6 , 57 temporomandibular disorder, 57 , 70 and shoulder impingement syndrome. 10 The most recent GWAS meta-analysis on 17 pain susceptibility traits reveals equal neuronal and immunological etiology for pain susceptibility. 51 …”

“…Existing GWASs for other chronic pain syndromes include back pain, 6,20,73 shoulder pain, 10,49 temporomandibular disorder (TMD), 66,70 multisite pain, [33][34][35] neuropathic pain, 55,64 and other chronic musculoskeletal pain conditions. 61,63,72,79 Functional analyses of these GWASs has provided critical information on the pathophysiology of chronic pain.…”

“…63 Finally, immune system genes were found to contribute to back pain, 6,57 temporomandibular disorder, 57,70 and shoulder impingement syndrome. 10 The most recent GWAS meta-analysis on 17 pain susceptibility traits reveals equal neuronal and immunological etiology for pain susceptibility. 51 Further analyses of different subclusters of human pain conditions have provided additional critical information on the pathophysiology of chronic pain.…”

Are commercial genetic injury tests premature?

“…87 Twenty-one polymorphisms within 19 genes or genetic regions have been reported to associate with rotator cuff injury in six studies using a GWAS approach (Table S7). [83][84][85][86][87][88] Most of the polymorphisms have been identified in a single publication analyzing a UK Biobank combined with either a meta-analysis including previous results or confirming the associations in another biobank or cohort. 84,87 Polymorphisms previously reported to associate with rotator cuff injury using a candidate gene approach were also valuated, and the association of three TNC polymorphisms were confirmed in one study but none of the other studies (Table S7).…”