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Sickle Cell Trait and Risk for Common Diseases: Evidence from the UK Biobank.

Joseph Hulsizer1, W Kyle Resurreccion1, Zhuqing Shi1

  • 1Program for Personalized Cancer Care, Evanston, Ill.

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|April 24, 2022
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Summary

Sickle cell trait (SCT) carriers have a higher risk of type 2 diabetes and related kidney and vascular diseases. This study highlights potential health risks associated with SCT, urging further investigation and awareness.

Keywords:
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Area of Science:

  • Genetics and Genomics
  • Epidemiology
  • Public Health

Background:

  • Sickle cell trait (SCT) is commonly considered benign, but emerging evidence suggests associations with various common diseases.
  • Previous studies on SCT and disease associations have yielded inconsistent results.
  • A comprehensive assessment of SCT's link to reported diseases in a large population cohort is warranted.

Purpose of the Study:

  • To systematically evaluate the associations between sickle cell trait and a range of reported diseases.
  • To investigate the prevalence and diagnostic accuracy of sickle cell trait in a large UK population.
  • To determine if SCT is an independent risk factor for common diseases, including diabetes and its complications.

Main Methods:

  • Utilized UK Biobank (UKB) data from self-reported Black individuals aged 40-69.
  • Determined sickle cell status via ICD-10 codes or HBB gene mutations.
  • Employed logistic regression to assess disease associations, adjusting for age, sex, and genetic principal components.

Main Results:

  • Sickle cell trait was identified in 8.72% of Black participants, with higher prevalence in females.
  • SCT was under-diagnosed, as most HBB gene Glu6Val carriers lacked an ICD-10 record.
  • SCT carriers showed significantly increased risks for type 2 diabetes (OR 1.38), renal diseases (including ESRD), and vascular diseases (including hypertension and stroke), with associations persisting after adjusting for diabetes.

Conclusions:

  • Sickle cell trait is significantly associated with an elevated risk of type 2 diabetes.
  • SCT is also linked to increased risks of diabetes-related complications and comorbidities, including renal and vascular diseases.
  • The study underscores the importance of considering SCT in the risk assessment for common chronic diseases.