Miriam Fleur Moffatt - Selected Publications#

Reference 15:

Zhang Y, Willis-Owen SAG, Spiegel S, Lloyd CM, Moffatt MF*, Cookson WOCM*. The ORMDL3 Asthma Gene Regulates ICAM1 and has Multiple Effects on Cellular Inflammation. Am J Respir Crit Care Med. 2018 Oct 19. doi: 10.1164/rccm.201803-0438OC. [Epub ahead of print]] PMID: 30339462 * joint senior authors

Using a polyomic approach and epithelial cell line models including knock-out and over-expression of ORMD3 this paper has revealed that ORMDL3 gene regulates the expression of the receptor for human rhinovirus – ICAM1 and has important and multiple impacts on cellular inflammation.

Reference 25:

Demenais F, Margaritte-Jeannin P, Barnes KC, Cookson WOC, ……., Zhao JH, Moffatt MF, Ober C, Nicolae DL. Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks. Nat Genet. 2018 Jan;50(1):42-53. PMID: 29273806

The largest multi-ancestry meta-analysis of asthma GWASs to date initiated by myself and Bill Cookson and co-led with four others. Study resulted in 5 new asthma loci being identified and confirmation of nine known loci. Investigation of pleiotropy revealed previously un-reported large overlaps in genetic variants with autoimmune and inflammatory diseases.

Reference 32:

James PL, Cannon J, Barber CM, Crawford L, Hughes H, Jones M, Szram J, Cowman S, Cookson WOC, Moffatt MF*, Cullinan P*. Metal worker's lung: spatial association with Mycobacterium avium. Thorax. 2018 Feb;73(2):151-156. PMID: 28851756 * joint senior authors

A study investigating an outbreak of metal working fluid associated hypersensitivity pneumonitis (an occupational disease) and identifying for the first time mycobacteria to be the causal agent.

Reference 51:

Zhang Q, Cox M, Liang Z, Brinkmann F, Cardenas PA, Duff R, Bhavsar P, Cookson W, Moffatt M*, Chung KF*. Airway Microbiota in Severe Asthma and Relationship to Asthma Severity and Phenotypes. PLoS One. 2016 Apr 14;11(4):e0152724. PMID: 27078029 * joint senior authors

Following on from my publication Hilty et al. PMID: 20052417, a study examining the lung microbiome in different severities of asthma. Profiling of induced sputum confirmed original results for mild/moderate asthma but also identified and expansion of the Phylum Firmicutes; Genus Streptococcus spp. in those individuals with severe corticosteroid resistant asthma.

Reference 58:

Liang L, Willis-Owen SA, Laprise C, Wong KC, Davies GA, Hudson TJ, Binia A, Hopkin JM, Yang IV, Grundberg E, Busche S, Hudson M, Rönnblom L, Pastinen TM, Schwartz DA, Lathrop GM*, Moffatt MF*, Cookson WO*. An epigenome-wide association study of total serum immunoglobulin E concentration. Nature. 2015;520(7549):670-4. PMID: 25707804 * joint senior author

To date the only epigenome-WAS for asthma and its associated traits. The study identified a number of epigenetic markers in key genes associated with eosinophil activation in relation to the atopic component of asthma. Markers include IL5 and IL5R which the current portfolio of new biologics are targeted against.

Reference 65:

Molyneaux PL, Cox MJ, Willis-Owen SA, Mallia P, Russell KE, Russell AM, Murphy E, Johnston SL, Schwartz DA, Wells AU, Cookson WO*, Maher TM*, Moffatt MF*. The Role of Bacteria in the Pathogenesis and Progression of Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2014; 190(8):906-13. * joint senior author

This study not only characterised the respiratory microbiome in idiopathic pulmonary fibrosis (IPF) but also revealed that level of bacterial burden predicated lung function and death independent of the genetic association with the MUC5B gene.

Reference 117:

Moffatt MF*, Gut IG*, Demenais F*, Strachan DP, Bouzigon E, Heath S, von Mutius E, Farrall M, Lathrop M, Cookson WO; GABRIEL Consortium. A large-scale, consortium-based genomewide association study of asthma. N Engl J Med. 2010;363(13):1211-21. PMID: 20860503 * joint first author

A European funded collaborative effort (GWAS) that identified the genetic factors underpinning asthma considering both childhood onset and adult onset asthma. Particular noteworthy as it showed that all the important asthma loci underlying the disease are concentrated in the respiratory epithelium. I was joint leader of this effort with Bill Cookson.

Reference 121:

Hilty M, Burke C, Pedro H, Cardenas P, Bush A, Bossley C, Davies J, Ervine A, Poulter L, Pachter L, Moffatt MF, Cookson WO. Disordered microbial communities in asthmatic airways. PLoS One. 2010;5(1):e8578. PMID: 20052417

This was the first paper using 16S rRNA amplicon cloning and sequencing to reveal that the healthy lungs are not sterile and have a characteristic microbiome that is altered (so called dysbiosis) in both asthma and chronic obstructive pulmonary disease (COPD).

Reference 135:

Dixon AL*, Liang L*, Moffatt MF*, Chen W, Heath S, Wong KC, Taylor J, Burnett E, Gut I, Farrall M, Lathrop GM, Abecasis GR, Cookson WO. A genome-wide association study of global gene expression. Nat Genet. 2007;39(10):1202-7. PMID: 17873877 * joint first author

This paper showed the value of global gene expression data in understanding complex disease genetics. It was used as the exemplar for eWAS and the GTEx Roadmap by Francis Collins and the data set has been utilised by many others in the complex genetics field including the 1000 genomes project.

Reference 136:

Moffatt MF*, Kabesch M*, Liang L*, Dixon AL, Strachan D, Heath S, Depner M, von Berg A, Bufe A, Rietschel E, Heinzmann A, Simma B, Frischer T, Willis-Owen SA, Wong KC, Illig T, Vogelberg C, Weiland SK, von Mutius E, Abecasis GR, Farrall M, Gut IG, Lathrop GM, Cookson WO. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature. 2007;448(7152):470-3. PMID: 17611496 * joint first author

This was the very first genome wide association study (GWAS) for doctor diagnosed childhood asthma involving ~1000 case and ~1000 matched controls. It resulted in the identification of the ORMDL3 gene (chromosome 17q) association. This gene is now recognised to be the strongest known genetic factor underlying asthma.