A study of 62.5 million people reveals what broad ethnic labels miss about rare diseases

Researchers examined millions of NHS health records to investigate how ethnicity relates to rare disease prevalence and why recorded COVID-19 infections differ between communities.

Study: Prevalence of 406 rare diseases by ethnicity and recorded COVID-19 infection rates among 62.5 million people in England. Image Credit: vetre / Shutterstock

In a recent study published in the journal Scientific Reports, researchers estimated the prevalence of 406 clinically curated rare diseases across ethnic groups in England and described recorded coronavirus disease 2019 (COVID-19) infection rates among people with these conditions. The analysis found that broad ethnic categories concealed substantial differences in recorded rare disease prevalence between communities.

Background

More than 6,000 rare diseases collectively affect approximately 3.5% to 5.9% of the global population, yet their individual rarity makes accurate population-level estimates difficult. Many rare diseases appear in childhood and have genetic causes. People from minoritized ethnic backgrounds may experience longer diagnostic journeys, more frequent misdiagnosis, and reduced access to specialist services. In addition, broad ethnic classifications may mask variations in rare diseases, making it difficult to identify differences in disease prevalence and recorded infection rates between communities.

About the study

The researchers conducted a cross-sectional study using linked electronic health records (EHRs) for individuals registered with general practices in England who were alive on July 31, 2023. Data were accessed through the National Health Service (NHS) England Secure Data Environment via the British Heart Foundation Data Science Centre’s CVD-COVID-UK/COVID-IMPACT Consortium. The study combined primary care records from the General Practice Extraction Service Data for Pandemic Planning and Research, hospital records from Hospital Episode Statistics for admitted patients and outpatients, and mortality records from the Office for National Statistics (ONS).

The researchers identified 406 rare diseases using diagnostic codes in the International Classification of Diseases (ICD-10) and Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT). The study considered diagnoses recorded between January 1, 1990, and July 31, 2023. The analysis estimated point prevalence among people alive on the study date, rather than the incidence of new diagnoses. Ethnicity was classified using six broad ONS categories and 19 more detailed NHS categories. The researchers calculated age- and sex-standardized prevalence using the 2021 England Census population as the reference. Odds ratios were calculated to assess demographic differences for 227 diseases with at least 100 affected individuals. Unlike the prevalence estimates, these odds ratios were not adjusted for age, deprivation, or other potential confounders.

COVID-19 infection was identified using positive polymerase chain reaction or lateral flow device test results recorded through July 31, 2023. Analyses were descriptive, and data were anonymized and disclosure-controlled before release.

Study results

The study included 62,539,740 individuals in England, of whom 1,051,470 (1.7%) had at least one of the 406 rare diseases. This percentage applies to the selected conditions, not all rare diseases. Compared with the population without a rare disease, affected individuals were more likely to be female (54.7% vs. 49.9%) and had a higher median age at the time of the study (46 vs. 40 years). Most affected individuals had one rare disease. Among affected individuals, the largest category was “Other” (77.8%), followed by cardiovascular conditions (18.9%), mixed categories (2.3%), and metabolic conditions (1.0%).

Age- and sex-standardized prevalence varied considerably, from fewer than one case per million people for the rarest conditions to 3,139.5 per million for polymyalgia rheumatica. Interatrial communication was the second most prevalent condition, at 2,449.7 per million, followed by infantile apnea, at 1,057.5 per million. These estimates demonstrate the substantial variation in the population prevalence of individual rare diseases.

Ethnic differences became more apparent when researchers compared detailed ethnic classifications rather than broad categories. Among the six ONS groups, polymyalgia rheumatica was most prevalent in the White group, whereas interatrial communication was most prevalent in the Mixed group. Within the more detailed NHS categories, interatrial communication was most prevalent among people of White and Caribbean backgrounds, at 3,721.5 per million, compared with 2,372.1 per million among those of White and African backgrounds.

Of the 227 diseases assessed for demographic differences, 104 showed significantly different odds in Asian or Asian British individuals compared with White individuals. Odds were higher for 38 conditions, including lamellar ichthyosis and maple syrup urine disease, and lower for 66. Among Black or Black British individuals, 83 diseases differed from the White group: 28 had higher odds, including Moyamoya disease, and 55 had lower odds.

Prevalence and COVID-19 infection rate of the top 25 rare diseases. Forest plot showing age- and sex-standardized prevalence (A) and COVID-19 infection rates (B) for the 25 most common rare diseases among 62.5 million individuals in England (study end date: 31 July 2023). Panel (A): Prevalence per million population, standardized to the 2021 England Census population. Panel (B) Percentage of patients with documented SARS-CoV-2 infection during the pandemic period. Colors indicate COVID-19 infection-rate categories: green = low (< 30%), yellow = medium (30–50%), red = high (> 50%). Vertical reference lines at 30% and 50% aid interpretation. Four diseases showed low infection rates: polymyalgia rheumatica (27.1%), infantile apnoea (29.9%), congenital laryngomalacia (24.6%), and retinopathy of prematurity (26.5%). All other diseases showed medium rates (30–50%). Diseases are ranked by prevalence (Panel A) and displayed in the same order across both panels for direct comparison.

The detailed classifications also revealed distinct patterns within individual communities. Pakistani individuals had higher odds of medium-chain acyl-coenzyme A dehydrogenase deficiency, dextrocardia, congenital laryngomalacia, and retinopathy of prematurity than White British individuals. Bangladeshi individuals also had higher odds of recorded Kawasaki disease and retinopathy of prematurity. The odds of discoid lupus erythematosus were higher for Black Caribbean individuals, while Black African individuals had lower odds of the same condition compared with White British individuals. Kawasaki disease also showed elevated odds across the analyzed mixed-ethnicity groups. Sex-related differences were observed, with males having higher odds of Legg-Calvé-Perthes disease and females having higher odds of several inflammatory conditions, including discoid lupus erythematosus.

COVID-19 infection was recorded in 32.8% of individuals with rare diseases, compared with 29.0% of those without rare diseases. Within the rare disease group, infection rates were highest among White British individuals (33.7%) and the broad White group (33.5%). Rates were lower among Black African (23.8%), Gypsy or Irish Traveler (24.1%), Bangladeshi (27.2%), and Pakistani (27.7%) individuals. These unadjusted figures describe documented positive tests, not all infections, and may reflect differences in age, disease composition, protective behaviors, and testing practices. Among the 25 most prevalent rare diseases, recorded infection rates ranged from 24.6% to 41.2%. Congenital laryngomalacia had the lowest rate (24.6%), followed by retinopathy of prematurity (26.5%), polymyalgia rheumatica (27.1%), and infantile apnea (29.9%).

Conclusions

The study provides national estimates of 406 selected rare diseases across ethnic groups in England and describes recorded COVID-19 infection among affected individuals. Detailed ethnic classifications revealed substantial differences that broad categories concealed, highlighting the importance of recognizing variation between communities. Recorded infection rates were higher among individuals with rare diseases than among those without these conditions, but rates varied by ethnicity and disease. These patterns may reflect differences in disease mix, age, healthcare access, diagnosis, and testing. These findings should be interpreted cautiously because diagnoses and infections depended on recorded healthcare data, the ethnic odds ratios were unadjusted, and the analyses cannot establish causation.

Source:

Journal reference:

- Gu, Q., Hasheminasab, S. A., Pineda-Moncusí, M., Chilala, C., Thygesen, J. H., Wu, H., Khalid, S., & CVD-COVID-UK/COVID-IMPACT Consortium. (2026). Prevalence of 406 rare diseases by ethnicity and recorded COVID-19 infection rates among 62.5 million people in England. Scientific Reports. DOI: 10.1038/s41598-026-70531-4, https://www.nature.com/articles/s41598-026-70531-4