Home page for Paul McKeigue

This is my personal web page. Larger files, including software packages and public datasets, can be found on my research group’s home page on my server.

My position

For the Usher Institute, information about research is on this page, information about taught postgraduate courses is on this page, and information about PhDs is on this page. I am on the Academic Steering Group of the Precision Medicine Doctoral Training Programme funded by the the MRC. I am a listed supervisor for the UKRI Centre for Doctoral Training in Biomedical Artificial Intelligence, which offers a four-year training program with the first year spent working for a Master’s degree through taught courses and projects, followed by a three-year PhD programme.

In the Usher Institute I am a member of the Molecular Epidemiology Group. I am a member of the Executive Group of the Centre for Statistics based in the School of Mathematics.

Since 2019 I have been on the Medical Research Council’s Methodology Research Programme (now renamed Better Methods Better Research) panel. Since June 2020 I have also been on a UKRI MRC COVID-19 Research & Innovation Panel reviewing applications submitted under the COVID-19 Rapid Response Rolling Call. I have briefed the NERVTAG (New and Emerging Respiratory Viruses Threat Assessment Group) panel on work that I have done in Public Health Scotland.

My writings and comments in the media on COVID-19 are in a personal capacity, except for research papers and reports where my affiliation is given as Public Health Scotland.

Contact details

Usher Institute of Population Health Sciences and Informatics
University of Edinburgh Medical School,
Teviot Place, Edinburgh EH8 9AG
Phone +44 131 650 4556


PGP public key associated with this email address:

1024D/B2D6769A 2013-07-11 Paul McKeigue <####.########@ed.ac.uk>
Fingerprint=683E 7E3B E8B3 83BB 8F80 363A A034 3F3B B2D6 769A

PGP public keys can be imported from keyservers such as http://keys.gnupg.net/

If you need to transfer large data files securely, I can set up an SFTP account for you on my server. You will need to use SSH public key authentication. Instructions for setting this up on a Windows PC are here.

Research profile

My research focuses on methods for molecular and genetic epidemiology, with applications in clinical prediction and personalized medicine. These methods make use of Bayesian and computationally-intensive statistical methods, and machine learning methods for constructing predictors. I work closely with Helen Colhoun’s research group at the Centre for Genomic and Experimental Medicine in the Institute of Genetics and Molecular Medicine. This collaboration includes the development of an analysis platform based on deidentified electronic health records and the use of this platform to study drug safety and complications of diabetes.

Since April 2020 most of my time has been spent within the Epidemiology Research Cell of Public Health Scotland’s COVID-19 Health Protection Response. In this role I have led the design and analysis of REACT-SCOT, a rolling case-control study of all cases of COVID-19 in Scotland since the start of the epidemic with up to ten controls per case, matched for age, sex and general practice and linked to electronic health records. This study has been used to construct and validate a risk score for severe or fatal COVID-19, and to investigate the relation of severe COVID-19 to drug prescribing, occupation (health care workers and teachers), socioeconomic status and ethnicity. Other studies in progress include an investigation of the effectiveness of advising clinically vulnerable individuals to shield, and the severity of variant B.1.1.7 compared with the original strain.

Current research other than on COVID-19

My current research includes:

Current research funding

A list of other recent research grants is here

Published papers and preprints on COVID-19

  1. McKeigue PM, McAllister DA, Bishop J et al. Efficacy of COVID-19 vaccination in individuals designated as clinically extremely vulnerable in Scotland. F1000Research 2021, 10:663 (https://doi.org/10.12688/f1000research.53812.1)

  2. Anoop Shah, Ciara Gribben, Jennifer Bishop, Peter Hanlon, David Caldwell, Rachael Wood, Martin Reid, Jim McMenamin, David Goldberg, Diane Stockton, Sharon Hutchinson, Chris Robertson, Paul M McKeigue, Helen M Colhoun, David McAllister. Effect of vaccination on transmission of COVID-19: an observational study in healthcare workers and their households. medRxiv 2021.03.11.21253275; doi: https://doi.org/10.1101/2021.03.11.21253275

  1. McKeigue, P.M., McAllister, D.A., Caldwell, D. et al. Relation of severe COVID-19 in Scotland to transmission-related factors and risk conditions eligible for shielding support: REACT-SCOT case-control study. BMC Med 19, 149 (2021). https://doi.org/10.1186/s12916-021-02021-5
  1. Wood R, Thomson E, Galbraith R, Gribben C, Caldwell D, Bishop J, Reid M, Shah ASV, Templeton K, Goldberg D, Robertson C, Hutchinson SJ, Colhoun HM, McKeigue PM, McAllister DA. Sharing a household with children and risk of COVID-19: a study of over 300 000 adults living in healthcare worker households in Scotland. Arch Dis Child. 2021 Mar 18:archdischild-2021-321604. doi: 10.1136/archdischild-2021-321604. Epub ahead of print. PMID: 33737319.
  1. McKeigue PM, Kennedy S, Weir A, Bishop J, McGurnaghan SJ, McAllister D, Robertson C, Wood R, Lone N, Murray J, Caparrotta TM, Smith-Palmer A, Goldberg D, McMenamin J, Guthrie B, Hutchinson S, Colhoun HM; Public Health Scotland COVID-19 Health Protection Study Group. Relation of severe COVID-19 to polypharmacy and prescribing of psychotropic drugs: the REACT-SCOT case-control study. BMC Med. 2021 Feb 22;19(1):51. doi: 10.1186/s12916-021-01907-8. PMID: 33612113.
  1. Shah ASV, Wood R, Gribben C, Caldwell D, Bishop J, Weir A, Kennedy S, Reid M, Smith-Palmer A, Goldberg D, McMenamin J, Fischbacher C, Robertson C, Hutchinson S, McKeigue P, Colhoun H, McAllister DA. Risk of hospital admission with coronavirus disease 2019 in healthcare workers and their households: nationwide linkage cohort study. BMJ. 2020 Oct 28;371:m3582. doi: 10.1136/bmj.m3582. PMID: 33115726; PMCID: PMC7591828.
  1. McGurnaghan SJ, Weir A, Bishop J, Kennedy S, Blackbourn LAK, McAllister DA, Hutchinson S, Caparrotta TM, Mellor J, Jeyam A, O’Reilly JE, Wild SH, Hatam S, Höhn A, Colombo M, Robertson C, Lone N, Murray J, Butterly E, Petrie J, Kennon B, McCrimmon R, Lindsay R, Pearson E, Sattar N, McKnight J, Philip S, Collier A, McMenamin J, Smith-Palmer A, Goldberg D, McKeigue PM, Colhoun HM; Public Health Scotland COVID-19 Health Protection Study Group; Scottish Diabetes Research Network Epidemiology Group. Risks of and risk factors for COVID-19 disease in people with diabetes: a cohort study of the total population of Scotland. Lancet Diabetes Endocrinol. 2021 Feb;9(2):82-93. doi: 10.1016/S2213-8587(20)30405-8. Epub 2020 Dec 23. PMID: 33357491; PMCID: PMC7832778.
  1. McKeigue PM, Weir A, Bishop J, McGurnaghan SJ, Kennedy S, McAllister D, Robertson C, Wood R, Lone N, Murray J, Caparrotta TM, Smith-Palmer A, Goldberg D, McMenamin J, Ramsay C, Hutchinson S, Colhoun HM; Public Health Scotland COVID-19 Health Protection Study Group. Rapid Epidemiological Analysis of Comorbidities and Treatments as risk factors for COVID-19 in Scotland (REACT-SCOT): A population-based case-control study. PLoS Med. 2020 Oct 20;17(10):e1003374. doi: 10.1371/journal.pmed.1003374. PMID: 33079969; PMCID: PMC7575101.
  1. Risk of hospitalisation with COVID-19 among teachers compared to healthcare workers and other working-age adults. A nationwide case-control study Lynda Fenton, Ciara Gribben, David Caldwell, Sam Colville, Jennifer Bishop, Martin Reid, Jane White, Sharon Hutchinson, Christopher Robertson, Helen M Colhoun, Rachael Wood, Paul M McKeigue, David A McAllister. https://www.medrxiv.org/content/10.1101/2021.02.05.21251189v1
  1. Reply to a letter by Alwan et al. published in the Lancet on 15 October (posted on this website).
  1. Trajectory of COVID-19 epidemic in Europe. Marco Colombo, Joseph Mellor, Helen M Colhoun, M. Gabriela M.Gomes, Paul M McKeigue. medRxiv 2020.09.26.20202267.
  1. Evaluation of "stratify and shield" as a policy option for ending the COVID-19 lockdown in the UK. Paul M. McKeigue, Helen M Colhoun medRxiv 2020.04.25.20079913; doi: https://doi.org/10.1101/2020.04.25.20079913.

Other recent papers of wide interest

Other publications for which the final accepted manuscript is available under open access can be found by searching Edinburgh Research Explorer.

Tutorials and teaching notes

These pages include tutorials, lecture slides and teaching notes prepared when advising colleagues, students and other researchers

Recent slide presentations

Recent publications

  1. O’Reilly JE, Jeyam A, Caparrotta TM, Mellor J, Hohn A, McKeigue PM, McGurnaghan SJ, Blackbourn LAK, McCrimmon R, Wild SH, Petrie JR, McKnight JA, Kennon B, Chalmers J, Phillip S, Leese G, Lindsay RS, Sattar N, Gibb FW, Colhoun HM; Scottish Diabetes Research Network Epidemiology Group. Rising Rates and Widening Socioeconomic Disparities in Diabetic Ketoacidosis in Type 1 Diabetes in Scotland: A Nationwide Retrospective Cohort Observational Study. Diabetes Care. 2021 Jul 8:dc210689. doi: 10.2337/dc21-0689. Epub ahead of print. PMID: 34244330.

  2. McGurnaghan SJ, McKeigue PM, Read SH, Franzen S, Svensson AM, Colombo M, Livingstone S, Farran B, Caparrotta TM, Blackbourn LAK, Mellor J, Thoma I, Sattar N, Wild SH, Gudbjörnsdottir S, Colhoun HM; Swedish National Diabetes Register and the Scottish Diabetes Research Network Epidemiology Group. Development and validation of a cardiovascular risk prediction model in type 1 diabetes. Diabetologia. 2021 Jun 9. doi: 10.1007/s00125-021-05478-4. Epub ahead of print. PMID: 34106282.

  3. Jeyam A, Gibb FW, McKnight JA, Kennon B, O’Reilly JE, Caparrotta TM, Höhn A, McGurnaghan SJ, Blackbourn LAK, Hatam S, McCrimmon RJ, Leese G, Lindsay RS, Petrie J, Chalmers J, Philip S, Wild SH, Sattar N, McKeigue PM, Colhoun HM; Scottish Diabetes Research Network (SDRN) Epidemiology Group. Marked improvements in glycaemic outcomes following insulin pump therapy initiation in people with type 1 diabetes: a nationwide observational study in Scotland. Diabetologia. 2021 Mar 8. doi: 10.1007/s00125-021-05413-7. Epub ahead of print. PMID: 33686483.

  4. Höhn A, Jeyam A, Caparrotta TM, McGurnaghan SJ, O’Reilly JE, Blackbourn LAK, McCrimmon RJ, Leese GP, McKnight JA, Kennon B, Lindsay RS, Sattar N, Wild SH, McKeigue PM, Colhoun HM; Scottish Diabetes Research Network (SDRN) Epidemiology Group. The association of polypharmacy and high-risk drug classes with adverse health outcomes in the Scottish population with type 1 diabetes. Diabetologia. 2021 Feb 19. doi: 10.1007/s00125-021-05394-7. Epub ahead of print. PMID: 33608768.

  5. McGurnaghan SJ, Weir A, Bishop J, Kennedy S, Blackbourn LAK, McAllister DA, Hutchinson S, Caparrotta TM, Mellor J, Jeyam A, O’Reilly JE, Wild SH, Hatam S, Höhn A, Colombo M, Robertson C, Lone N, Murray J, Butterly E, Petrie J, Kennon B, McCrimmon R, Lindsay R, Pearson E, Sattar N, McKnight J, Philip S, Collier A, McMenamin J, Smith-Palmer A, Goldberg D, McKeigue PM, Colhoun HM; Public Health Scotland COVID-19 Health Protection Study Group; Scottish Diabetes Research Network Epidemiology Group. Risks of and risk factors for COVID-19 disease in people with diabetes: a cohort study of the total population of Scotland. Lancet Diabetes Endocrinol. 2021 Feb;9(2):82-93. doi: 10.1016/S2213-8587(20)30405-8. Epub 2020 Dec 23. PMID: 33357491; PMCID: PMC7832778.

  6. Jeyam A, Colhoun H, McGurnaghan S, Blackbourn L, McDonald TJ, Palmer CNA, McKnight JA, Strachan MWJ, Patrick AW, Chalmers J, Lindsay RS, Petrie JR, Thekkepat S, Collier A, MacRury S, McKeigue PM; SDRNT1BIO Investigators. Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications. Diabetes Care. 2020 Dec 10:dc200567. doi: 10.2337/dc20-0567. Epub ahead of print. PMID: 33303639.

  7. Colombo M, Shehni AA, Thoma I, McGurnaghan SJ, Blackbourn LAK, Wilkinson H, Collier A, Patrick AW, Petrie JR, McKeigue PM, Saldova R, Colhoun HM. Quantitative levels of serum N-glycans in type 1 diabetes and their association with kidney disease. Glycobiology. 2020 Nov 27:cwaa106. doi: 10.1093/glycob/cwaa106. Epub ahead of print. PMID: 33245334.

  8. Shah ASV, Wood R, Gribben C, Caldwell D, Bishop J, Weir A, Kennedy S, Reid M, Smith-Palmer A, Goldberg D, McMenamin J, Fischbacher C, Robertson C, Hutchinson S, McKeigue P, Colhoun H, McAllister DA. Risk of hospital admission with coronavirus disease 2019 in healthcare workers and their households: nationwide linkage cohort study. BMJ. 2020 Oct 28;371:m3582. doi: 10.1136/bmj.m3582. PMID: 33115726; PMCID: PMC7591828.

  9. McKeigue PM, Weir A, Bishop J, McGurnaghan SJ, Kennedy S, McAllister D, Robertson C, Wood R, Lone N, Murray J, Caparrotta TM, Smith-Palmer A, Goldberg D, McMenamin J, Ramsay C, Hutchinson S, Colhoun HM; Public Health Scotland COVID-19 Health Protection Study Group. Rapid Epidemiological Analysis of Comorbidities and Treatments as risk factors for COVID-19 in Scotland (REACT- SCOT): A population-based case-control study. PLoS Med. 2020 Oct 20;17(10):e1003374. doi: 10.1371/journal.pmed.1003374. PMID: 33079969; PMCID: PMC7575101.

  10. Štambuk J, Nakić N, Vučković F, Pučić-Baković M, Razdorov G, Trbojević- Akmačić I, Novokmet M, Keser T, Vilaj M, Štambuk T, Gudelj I, Šimurina M, Song M, Wang H, Salihović MP, Campbell H, Rudan I, Kolčić I, Eller LA, McKeigue P, Robb ML, Halfvarson J, Kurtoglu M, Annese V, Škarić-Jurić T, Molokhia M, Polašek O, Hayward C, Kibuuka H, Thaqi K, Primorac D, Gieger C, Nitayaphan S, Spector T, Wang Y, Tillin T, Chaturvedi N, Wilson JF, Schanfield M, Filipenko M, Wang W, Lauc G. Global variability of the human IgG glycome. Aging (Albany NY). 2020 Aug 12;12(15):15222-15259. doi: 10.18632/aging.103884. Epub 2020 Aug 12. PMID: 32788422; PMCID: PMC7467356.

  11. Marcovecchio ML, Colombo M, Dalton RN, McKeigue PM, Benitez-Aguirre P, Cameron FJ, Chiesa ST, Couper JJ, Craig ME, Daneman D, Davis EA, Deanfield JE, Donaghue KC, Jones TW, Mahmud FH, Marshall SM, Neil A, Colhoun HM, Dunger DB; AdDIT and the SDRNT1BIO Investigators. Biomarkers associated with early stages of kidney disease in adolescents with type 1 diabetes. Pediatr Diabetes. 2020 Aug 11. doi: 10.1111/pedi.13095. Epub ahead of print. PMID: 32783254.

  12. Cherlin S, Lewis MJ, Plant D, Nair N, Goldmann K, Tzanis E, Barnes MR, McKeigue P, Barrett JH, Pitzalis C, Barton A; MATURA Consortium, Cordell HJ. Investigation of genetically regulated gene expression and response to treatment in rheumatoid arthritis highlights an association between IL18RAP expression and treatment response. Ann Rheum Dis. 2020 Nov;79(11):1446-1452. doi: 10.1136/annrheumdis-2020-217204. Epub 2020 Jul 30. PMID: 32732242; PMCID: PMC7569378.

    1. Barbu MC, Spiliopoulou A, Colombo M, McKeigue P, Clarke TK, Howard DM, Adams MJ, Shen X, Lawrie SM, McIntosh AM, Whalley HC. Expression quantitative trait loci-derived scores and white matter microstructure in UK Biobank: a novel approach to integrating genetics and neuroimaging. Transl Psychiatry. 2020 Feb 4;10(1):55. doi: 10.1038/s41398-020-0724-y. PMID: 32066731; PMCID: PMC7026054.
  13. O'Reilly JE, Blackbourn LAK, Caparrotta TM, Jeyam A, Kennon B, Leese GP, Lindsay RS, McCrimmon RJ, McGurnaghan SJ, McKeigue PM, McKnight JA, Petrie JR, Philip S, Sattar N, Wild SH, Colhoun HM; Scottish Diabetes Research Network Epidemiology Group. Time trends in deaths before age 50 years in people with type 1 diabetes: a nationwide analysis from Scotland 2004-2017. Diabetologia. 2020 Aug;63(8):1626-1636. doi: 10.1007/s00125-020-05173-w. Epub 2020 May 26. PMID: 32451572; PMCID: PMC7351819.

  14. Caparrotta TM, Blackbourn LAK, McGurnaghan SJ, Chalmers J, Lindsay R, McCrimmon R, McKnight J, Wild S, Petrie JR, Philip S, McKeigue PM, Webb DJ, Sattar N, Colhoun HM; Scottish Diabetes Research Network–Epidemiology Group. Prescribing Paradigm Shift? Applying the 2019 European Society of Cardiology-Led Guidelines on Diabetes, Prediabetes, and Cardiovascular Disease to Assess Eligibility for Sodium-Glucose Cotransporter 2 Inhibitors or Glucagon-Like Peptide 1 Receptor Agonists as First-Line Monotherapy (or Add-on to Metformin Monotherapy) in Type 2 Diabetes in Scotland. Diabetes Care. 2020 Jun 24:dc200120. doi: 10.2337/dc20-0120. Epub ahead of print. PMID: 32581068.

  15. Li X, Timofeeva M, Spiliopoulou A, McKeigue P, He Y, Zhang X, Svinti V, Campbell H, Houlston RS, Tomlinson IPM, Farrington SM, Dunlop MG, Theodoratou E. Prediction of colorectal cancer risk based on profiling with common genetic variants. Int J Cancer. 2020 Jul 7. doi: 10.1002/ijc.33191. Epub ahead of print. PMID: 32638365.

  16. Jeyam A, McGurnaghan SJ, Blackbourn LAK, McKnight JM, Green F, Collier A, McKeigue PM, Colhoun HM; SDRNT1BIO Investigators. Diabetic Neuropathy Is a Substantial Burden in People With Type 1 Diabetes and Is Strongly Associated With Socioeconomic Disadvantage: A Population-Representative Study From Scotland. Diabetes Care. 2020 Jan 23:dc191582. doi: 10.2337/dc19-1582. Epub ahead of print. PMID: 31974100.

  17. Colombo M, McGurnaghan SJ, Blackbourn LAK, Dalton RN, Dunger D, Bell S, Petrie JR, Green F, MacRury S, McKnight JA, Chalmers J, Collier A, McKeigue PM, Colhoun HM; Scottish Diabetes Research Network (SDRN) Type 1 Bioresource Investigators. Comparison of serum and urinary biomarker panels with albumin/creatinine ratio in the prediction of renal function decline in type 1 diabetes. Diabetologia. 2020 Jan 8:10.1007/s00125-019-05081-8. doi: 10.1007/s00125-019-05081-8. Epub ahead of print. PMID: 31915892.

  18. Colombo M, McGurnaghan SJ, Bell S, MacKenzie F, Patrick AW, Petrie JR, McKnight JA, MacRury S, Traynor J, Metcalfe W, McKeigue PM, Colhoun HM; Scottish Diabetes Research Network (SDRN) Type 1 Bioresource Investigators and the Scottish Renal Registry. Predicting renal disease progression in a large contemporary cohort with type 1 diabetes mellitus. Diabetologia. 2020 Mar;63(3):636-647. doi: 10.1007/s00125-019-05052-z. Epub 2019 Dec 5. PMID: 31807796.

  19. Li X, Meng X, He Y, Spiliopoulou A, Timofeeva M, Wei WQ, Gifford A, Yang T, Varley T, Tzoulaki I, Joshi P, Denny JC, Mckeigue P, Campbell H, Theodoratou E. Genetically determined serum urate levels and cardiovascular and other diseases in UK Biobank cohort: A phenome-wide mendelian randomization study. PLoS Med. 2019 Oct 18;16(10):e1002937. doi: 10.1371/journal.pmed.1002937. PMID: 31626644; PMCID: PMC6799886.

  20. Ochs A, McGurnaghan S, Black MW, Leese GP, Philip S, Sattar N, Styles C, Wild SH, McKeigue PM, Colhoun HM; Scottish Diabetes Research Network Epidemiology Group and the Diabetic Retinopathy Screening Collaborative. Use of personalised risk-based screening schedules to optimise workload and sojourn time in screening programmes for diabetic retinopathy: A retrospective cohort study. PLoS Med. 2019 Oct 17;16(10):e1002945. doi: 10.1371/journal.pmed.1002945. PMID: 31622334; PMCID: PMC6797087.

  21. Meng X, Li X, Timofeeva MN, He Y, Spiliopoulou A, Wei WQ, Gifford A, Wu H, Varley T, Joshi P, Denny JC, Farrington SM, Zgaga L, Dunlop MG, McKeigue P, Campbell H, Theodoratou E. Phenome-wide Mendelian-randomization study of genetically determined vitamin D on multiple health outcomes using the UK Biobank study. Int J Epidemiol. 2019 Oct 1;48(5):1425-1434. doi: 10.1093/ije/dyz182. PMID: 31518429; PMCID: PMC6857754.

  22. Salem RM, Todd JN, Sandholm N, Cole JB, Chen WM, Andrews D, Pezzolesi MG, McKeigue PM, Hiraki LT, Qiu C, Nair V, Di Liao C, Cao JJ, Valo E, Onengut- Gumuscu S, Smiles AM, McGurnaghan SJ, Haukka JK, Harjutsalo V, Brennan EP, van Zuydam N, Ahlqvist E, Doyle R, Ahluwalia TS, Lajer M, Hughes MF, Park J, Skupien J, Spiliopoulou A, Liu A, Menon R, Boustany-Kari CM, Kang HM, Nelson RG, Klein R, Klein BE, Lee KE, Gao X, Mauer M, Maestroni S, Caramori ML, de Boer IH, Miller RG, Guo J, Boright AP, Tregouet D, Gyorgy B, Snell-Bergeon JK, Maahs DM, Bull SB, Canty AJ, Palmer CNA, Stechemesser L, Paulweber B, Weitgasser R, Sokolovska J, Rovīte V, Pīrāgs V, Prakapiene E, Radzeviciene L, Verkauskiene R, Panduru NM, Groop LC, McCarthy MI, Gu HF, Möllsten A, Falhammar H, Brismar K, Martin F, Rossing P, Costacou T, Zerbini G, Marre M, Hadjadj S, McKnight AJ, Forsblom C, McKay G, Godson C, Maxwell AP, Kretzler M, Susztak K, Colhoun HM, Krolewski A, Paterson AD, Groop PH, Rich SS, Hirschhorn JN, Florez JC; SUMMIT Consortium, DCCT/EDIC Research Group, GENIE Consortium. Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen. J Am Soc Nephrol. 2019 Oct;30(10):2000-2016. doi: 10.1681/ASN.2019030218. Epub 2019 Sep 19. PMID: 31537649; PMCID: PMC6779358.

  23. McKeigue PM, Spiliopoulou A, McGurnaghan S, Colombo M, Blackbourn L, McDonald TJ, Onengut-Gomuscu S, Rich SS, A Palmer CN, McKnight JA, J Strachan MW, Patrick AW, Chalmers J, Lindsay RS, Petrie JR, Thekkepat S, Collier A, MacRury S, Colhoun HM. Persistent C-peptide secretion in Type 1 diabetes and its relationship to the genetic architecture of diabetes. BMC Med. 2019 Aug 23;17(1):165. doi: 10.1186/s12916-019-1392-8. PubMed PMID: 31438962.

  24. Floyd JS, Bloch KM, Brody JA, Maroteau C, Siddiqui MK, Gregory R, Carr DF, Molokhia M, Liu X, Bis JC, Ahmed A, Liu X, Hallberg P, Yue QY, Magnusson PKE, Brisson D, Wiggins KL, Morrison AC, Khoury E, McKeigue P, Stricker BH, Lapeyre-Mestre M, Heckbert SR, Gallagher AM, Chinoy H, Gibbs RA, Bondon-Guitton E, Tracy R, Boerwinkle E, Gaudet D, Conforti A, van Staa T, Sitlani CM, Rice KM, aitland-van der Zee AH, Wadelius M, Morris AP, Pirmohamed M, Palmer CAN, Psaty BM, Alfirevic A; PREDICTION-ADR Consortium and EUDRAGENE. Pharmacogenomics of statin-related myopathy: Meta-analysis of rare variants from whole-exome sequencing. PLoS One. 2019 Jun 26;14(6):e0218115. doi: 10.1371/journal.pone.0218115. eCollection 2019. PubMed PMID: 31242253; PubMed Central PMCID: PMC6594672.

  25. Colombo M, Valo E, McGurnaghan SJ, Sandholm N, Blackbourn LAK, Dalton RN, Dunger D, Groop PH, McKeigue PM, Forsblom C, Colhoun HM; FinnDiane Study Group and the Scottish Diabetes Research Network (SDRN) Type 1 Bioresource Collaboration. Biomarker panels associated with progression of renal disease in type 1 diabetes. Diabetologia. 2019 Jun 20. doi: 10.1007/s00125-019-4915-0. [Epub]

  26. Mair C, Wulaningsih W, Jeyam A, McGurnaghan S, Blackbourn L, Kennon B, Leese G, Lindsay R, McCrimmon RJ, McKnight J, Petrie JR, Sattar N, Wild SH, Conway N, Craigie I, Robertson K, Bath L, McKeigue PM, Colhoun HM; Scottish Diabetes Research Network (SDRN) Epidemiology Group. Glycaemic control trends in people with type 1 diabetes in Scotland 2004-2016. Diabetologia. 2019 Aug;62(8):1375-1384. doi: 10.1007/s00125-019-4900-7. Epub 2019 May 18. PubMed PMID: 31104095.

  27. Spiliopoulou A, Colombo M, Plant D, Nair N, Cui J, Coenen MJ, Ikari K, Yamanaka H, Saevarsdottir S, Padyukov L, Bridges SL Jr, Kimberly RP, Okada Y, van Riel PLC, Wolbink G, van der Horst-Bruinsma IE, de Vries N, Tak PP, Ohmura K, Canhão H, Guchelaar HJ, Huizinga TW, Criswell LA, Raychaudhuri S, Weinblatt ME, Wilson AG, Mariette X, Isaacs JD, Morgan AW, Pitzalis C, Barton A, McKeigue P. Association of response to TNF inhibitors in rheumatoid arthritis with quantitative trait loci for CD40 and CD39. Ann Rheum Dis. 2019 Apr 29. doi: 10.1136/annrheumdis-2018-214877. [Epub ahead of print] PubMed PMID: 31036624.

  28. Hensor EMA, McKeigue P, Ling SF, Colombo M, Barrett JH, Nam JL, Freeston J, Buch MH, Spiliopoulou A, Agakov F, Kelly S, Lewis MJ, Verstappen SMM, MacGregor AJ, Viatte S, Barton A, Pitzalis C, Emery P, Conaghan PG, Morgan AW. Validity of a two-component imaging-derived disease activity score for improved assessment of synovitis in early rheumatoid arthritis. Rheumatology (Oxford). 2019 Mar 1. doi: 10.1093/rheumatology/kez049. [Epub ahead of print] PubMed PMID: 30824919.

  29. McGurnaghan SJ, Brierley L, Caparrotta TM, McKeigue PM, Blackbourn LAK, Wild SH, Leese GP, McCrimmon RJ, McKnight JA, Pearson ER, Petrie JR, Sattar N, Colhoun HM; Scottish Diabetes Research Network Epidemiology Group. The effect of dapagliflozin on glycaemic control and other cardiovascular disease risk factors in type 2 diabetes mellitus: a real-world observational study. Diabetologia. 2019 Apr;62(4):621-632. doi: 10.1007/s00125-018-4806-9. Epub 2019 Jan 10. PubMed PMID: 30631892.

  30. Colombo M, Looker HC, Farran B, Hess S, Groop L, Palmer CNA, Brosnan MJ,Dalton RN, Wong M, Turner C, Ahlqvist E, Dunger D, Agakov F, Durrington P,ivingstone S, Betteridge J, McKeigue PM, Colhoun HM; SUMMIT Investigators. Serum kidney injury molecule 1 and β(2)-microglobulin perform as well as larger biomarker panels for prediction of rapid decline in renal function in type 2 diabetes. Diabetologia. 2018 Oct 5. doi: 10.1007/s00125-018-4741-9. [Epub ah.pead of print] PubMed PMID: 30288572.

  31. Cherlin S, Plant D , Taylor JC, Colombo M, Spiliopoulou A , Tzanis E , Morgan AW, Barnes MR , McKeigue P, Barrett JH, Pitzalis C, Barton A, MATURA Consortium, Cordell HJ. Prediction of treatment response in rheumatoid arthritis patients using genome-wide SNP data. Genetic Epidemiology 2018: Dec;42(8):754-771. doi: 10.1002/gepi.22159

  32. Massey J, Plant D, Hyrich K, Morgan AW, Wilson AG, Spiliopoulou A, Colombo M, McKeigue P, Isaacs J, Cordell H, Pitzalis C, Barton A; BRAGGSS, MATURA Consortium. Genome-wide association study of response to tumour necrosis factor inhibitor therapy in rheumatoid arthritis. Pharmacogenomics J. 2018 Aug 31. doi: 10.1038/s41397-018-0040-6. [Epub ahead of print] PubMed PMID: 30166627.

  33. McKeigue P. Quantifying performance of a diagnostic test as the expected information for discrimination: Relation to the C-statistic. Stat Methods Med Res. 2018 Jan 1:962280218776989. doi: 10.1177/0962280218776989. [Epub ahead of print] PubMed PMID: 29978758.

  34. Colombo M,, Looker HC, Farran B, Agakov F, Brosnan MJ, Welsh P, Sattar N, Livingston SJ, Durrington PN, Betteridge DJ, McKeigue PM, Colhoun HM. Apolipoprotein CIII and N-Terminal Prohormone B-type Natriuretic Peptide as Independent Predictors for Cardiovascular Disease in Type 2 Diabetes. Atherosclerosis 2018, May 21;274:182-190

  35. McKeigue P. Sample size requirements for learning to classify with high-dimensional biomarker panels. Stat Methods Med Res. 2018 Jan 1:962280217738807. doi: 10.1177/0962280217738807. [Epub ahead of print] PubMed PMID: 29179643

Software

Sample size calculations for learning to classify with biomarker panels

To calculate the required sample size for learning to predict from high-dimensional biomarker panels, classical statistical power calculations are not very useful. What researchers really need is a learning curve, showing how the expected predictive performance of the trained model depends on the size of the training sample from which this model is learned.

I have described a simple method for calculating the sample size required to learn to classify with a high-dimensional biomarker panel, based on the asymptotic distribution of the weight of evidence (log Bayes factor) in a recent paper: Sample size requirements for learning to classify with high-dimensional biomarker panels (Statistical Methods for Medical Research 2017, final version now on PubMed). The assumptions underlying this method are:-

The method is implemented in an online sample size calculator, written with the R shiny package and deployed at https://pmckeigue.shinyapps.io/sampsizeapp/.

To use it, move the sliders to specify:-

Then click the “Submit” button


The table generated by the app has three columns:

  1. the expectation of the information for discrimination extracted by the trained model, as a percentage of the information for discrimination extracted by the optimal model that would be learned from a sample of infinite size. This is scaled from 25% to 90%.

  2. the C-statistic corresponding to these values of expected information for discrimination.

  3. the ratio of cases to variables, assuming a balanced study design with equal numbers of cases and controls.

The app also plots a learning curve, showing how the expected information for discrimination and C-statistic obtained with the trained model depends on the ratio of cases to variables. In this example, where the optimal model has an expected discrimination of 1 bit equivalent to a C-statistic of 0.80, and 1% of biomarkers have nonzero effects, a sample size of at least 0.1 cases per variable is required to learn a model that has expected information for discrimination 60% of that obtained with the optimal model.



Links relevant to “zero COVID” disease elimination strategies

These brief notes provide links to material relevant to disease elimination as a possible strategy for COVID-19 in Scotland.

“I am very much in the elimination camp on this - get it as low as we can to open up as much normality and give us the best chance of controlling it.”

The Scottish Government should implement an elimination strategy as far as possible in 2021 and where this is not feasible should aim for maximum suppression of the virus.

“We can see countries striving very hard for elimination and getting there and then they get little blips. So you saw this week in Melbourne some people might have been watching the tennis with a crowd and then no crowd. So six days, five days of lockdown because they got a few cases. So elimination is not eradicating the virus. The virus, in order to be completely eradicated, would be a smallpox-style, many years project, and the virus would probably have to help us. But we can strive for elimination.”

Zero Covid envisages a total reconstruction of our way of life – diet, housing, relations with other species, travel and work, enforced by micro-management and aggressive policing. Like all utopians, its advocates think the ends justify whatever means are required to achieve them.

Over time, scientists expect COVID-19 to become endemic, meaning the virus will reach a stable, and hopefully manageable level.

vaccines open a path from the elimination approach advocated by many in earlier phase, to an ability to manage Covid differently and less restrictively.