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Neil McHugh

Publications and source records attributed to Neil McHugh.

7 recordsLinked to original sources
PubMed2025

Genetic Architecture of Idiopathic Inflammatory Myopathies From Meta-Analyses.

OBJECTIVE: Idiopathic inflammatory myopathies (IIMs, myositis) are rare systemic autoimmune disorders that lead to muscle inflammation, weakness, and extramuscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome-wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome-wide myositis studies and analyzed the largest myositis data set to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes. METHODS: We performed association analyses on 14,903 individuals (3,206 patients and 11,697 controls) with genotypes and imputed data from the Trans-Omics for Precision Medicine reference panel. Fine-mapping and expression quantitative trait locus colocalization analyses in myositis-relevant tissues indicated potential causal variants. Functional annotation and network analyses using the random walk with restart (RWR) algorithm explored underlying genetic networks and drug repurposing opportunities. RESULTS: Our analyses identified novel risk loci and susceptibility genes, such as FCRLA, NFKB1, IRF4, DCAKD, and ATXN2 in overall IIMs; NEMP2 in polymyositis; ACBC11 in dermatomyositis; and PSD3 in myositis with anti-histidyl-transfer RNA synthetase autoantibodies (anti-Jo-1). We also characterized effects of HLA region variants and the role of C4. Colocalization analyses suggested putative causal variants in DCAKD in skin and muscle, HCP5 in lung, and IRF4 in Epstein-Barr virus (EBV)-transformed lymphocytes, lung, and whole blood. RWR further prioritized additional candidate genes, including APP, CD74, CIITA, NR1H4, and TXNIP, for future investigation. CONCLUSION: Our study uncovers novel genetic regions contributing to IIMs, advancing our understanding of myositis pathogenesis and offering new insights for future research.

Humans↗
PubMed2006

Developing classification criteria for peripheral joint psoriatic arthritis. Step I. Establishing whether the rheumatologist's opinion on the diagnosis can be used as the "gold standard".

OBJECTIVE: The study of psoriatic arthritis (PsA) is hampered by the absence of a widely accepted, validated case definition. We investigated whether the physician's opinion can be used as a gold standard when developing classification criteria for peripheral joint PsA. METHODS: UK rheumatologists who had published on PsA and attendees at 3 international meetings on PsA held in the UK were polled by questionnaire. There were 3 phases. The first questionnaire asked whether rheumatologists believed in the construct of PsA. The second survey developed a list of features thought to distinguish patients with PsA from other forms of peripheral arthritis. The final phase was development of a series of 61 "paper" patients with various combinations of the features of PsA. The paper patients were assessed by 15 rheumatologists who were asked whether, in their opinion, the patient had PsA. Latent class analysis was used to identify subgroups of patients and cross-tabulations were used to identify which clinical and laboratory features were associated with each subgroup. RESULTS: Rheumatologists agreed on the construct of PsA and that not all patients with psoriasis and an inflammatory polyarthritis have PsA. Latent class analysis identified 3 classes, corresponding to definite PsA; a middle group that was very likely to be given a diagnosis of PsA by some rheumatologists (high diagnosers), but unlikely to be given the diagnosis by others (low diagnosers); and a third group corresponding to "probably not PsA." CONCLUSION: For the group of patients with "definite PsA" the physician's opinion can be taken as the gold standard when developing classification criteria. However, for patients in the "middle group" there will always be disagreement with the gold standard whether the standard is based on the opinion of the high diagnosers or the low diagnosers.

Arthritis, Psoriatic↗
PubMed2006

Endothelin axis polymorphisms in patients with scleroderma.

OBJECTIVE: To evaluate the distribution of polymorphisms in the endothelin 1 (EDN1), endothelin receptor A (EDNRA) and endothelin receptor B (EDNRB) genes in systemic sclerosis (SSc; scleroderma) and SSc subsets. METHODS: Two hundred five patients with SSc and 255 healthy controls were screened for polymorphisms in EDN1, EDNRA, and EDNRB, using sequence-specific primer-polymerase chain reaction. The polymorphisms studied were at the following positions: for EDN1, -1370 (T-1370G) of the promoter, +138 of exon 1 (+138 A/-), +85 of exon 3 (E106E), and +23 of exon 5 (K198N); for EDNRA, -231 of exon 1 (G-231A), and +69(H323H) and +105 (E335E) of exon 6; for EDNRB, +2841 of exon 2 (EDNRB-3), -2547 of exon 3 (EDNRB-2), and -2446 of exon 3 (EDNRB-1). RESULTS: No significant differences between the SSc group as a whole and control subjects were observed for any of the investigated polymorphisms in EDN1, EDNRA, and EDNRB. However, compared with patients with limited cutaneous SSc, patients with diffuse skin involvement had an increased frequency of allele carriage of EDNRB-1A (76.8% versus 54.4%; P = 0.002), EDNRB-2A (79.7% versus 60.2%; P = 0.006), and EDNRB-3G (79.7% versus 56.6%; P = 0.001). Significantly increased carriage frequencies for EDNRA alleles H323H/C and E335E/A were observed in SSc patients with anti-RNA polymerase (anti-RNAP) antibodies, compared with both anti-RNAP-negative SSc patients (P < 0.05) and control subjects (P < 0.005). CONCLUSION: The finding of associations between endothelin receptors A and B and distinct clinical and immunologic SSc subsets supports the role of endothelin and its receptors in the pathogenesis of SSc. However, these findings and their functional significance need to be confirmed and investigated in future studies.

Endothelins↗
PubMed2006

Revised British Isles Lupus Assessment Group 2004 index: a reliable tool for assessment of systemic lupus erythematosus activity.

OBJECTIVE: To test the interrater reliability of the revised British Isles Lupus Assessment Group 2004 (BILAG-2004) index for the assessment of systemic lupus erythematosus (SLE) activity. METHODS: Patients with SLE were recruited from 11 centers. Two physician raters separately assessed the patients' disease activity using the BILAG-2004 index in routine clinical practice. Scores ranged from A (for very active disease) to E (for inactivity). Two reliability exercises were performed. Changes were made to the index after the first exercise (E1), and additional training was provided to the raters before the second exercise (E2). E1 and E2 involved 12 and 14 raters, respectively. Interrater reliability was assessed using kappa statistics and intraclass correlation coefficients. Levels of agreement and the extent of major disagreement were also examined. Major disagreement was defined as a score difference between raters of A versus C, D, or E or B versus D or E. RESULTS: For each exercise, 97 patients were recruited. In E1, the mean age of the patients was 42.3 years (range 18.5-82.2 years), 89.7% were women, and 74.2% were white, 8.2% were Afro-Caribbean, and 13.4% were South Asian, and in E2, the mean age was 43.7 years (range 17.7-75 years), 90.7% were women, and 68% were white, 15.5% were Afro-Caribbean, and 11.3% were South Asian. The mean disease duration was 9.4 years (range 0-32.1 years) for patients in E1 and 10 years (range 0-34.8 years) in E2. There was improvement in the interrater reliability and the level of agreement from E1 to E2. Further improvement was achieved after removal of poorly performing items. CONCLUSION: The BILAG-2004 index is a reliable tool to assess SLE activity. The use of a well-defined glossary and training of raters are essential to ensure the optimal performance of the index.

Activities of Daily Living↗
PubMed2005

Genetic factors in psoriatic arthritis.

The genetic factors that are associated with psoriatic arthritis (PsA) are intricately linked with those that predispose to psoriasis itself. The strongest association is with human leukocyte antigen-Cw*0602, although true susceptibility may lie with one of the neighboring genes along a disease-associated haplotype. There are a number of interesting candidate genes within the major histocompatibility complex (MHC) region with strong functional relevance that have been investigated in PsA. In addition, several areas outside the MHC complex have been highlighted as a result of genetic linkage studies in psoriasis. PsA is a complex, multifactorial disease where multiple genes are likely to influence disease susceptibility, severity, and clinical phenotype. The current evidence for genetic factors in psoriasis and PsA will be reviewed.

Arthritis, Psoriatic↗
PubMed2003

The Influence of the HLA-DRB1 rheumatoid arthritis shared epitope on the clinical characteristics and radiological outcome of psoriatic arthritis.

OBJECTIVE: To investigate the associations of the HLA-DRB1 rheumatoid arthritis shared epitope (SE) with clinical characteristics and radiological outcome in patients with psoriatic arthritis (PsA). METHODS: One hundred fifty-eight patients with well documented PsA and 250 controls were typed for HLA-DRB1 alleles including the SE by polymerase chain reaction. Clinical data collected on the patient group included disease subset, swollen and tender joint counts, the psoriasis area severity index (PASI), and the presence of radiological erosions. Clinical and radiological associations with HLA-DRB1 and SE alleles were determined. RESULTS: There was an increased frequency of HLA-DR7 (41 vs 25%; puncorr = 0.001, OR 2.02, pcorr = 0.01) and a decreased frequency of HLA-DR2 (19 vs 28%; puncorr = 0.03, OR 0.59, pcorr = 0.3) in the patient population compared with controls. There was no significant difference in the frequency of HLA-DR1 and HLA-DR4 between patient and control populations. There was no significant difference in the prevalence of SE alleles between the patient and control populations (48 vs 54%). There was no increase in the prevalence of the SE in the polyarthritis subgroup, but there was a marginal decrease in those who remained in the oligoarthritis subgroup. There were no differences with respect to sex, age of onset of disease, family history, Health Assessment Questionnaire score, joint score, skin score, or nail score between those patients who were SE positive and those who were SE negative. However, significantly more patients who were SE positive developed radiological erosions (60 vs 43%; p = 0.03, OR 2.11). CONCLUSION: Overall, the prevalence of the SE in patients with PsA did not differ from our control population. However, it was overrepresented in those who developed radiological erosions. It is possible that the SE does have a role in the clinical severity of PsA.

Adult↗