Publication: European Journal of Epidemiology

Stephen Burgess, Sonja A Swanson & Jeremy A Labrecque

21 February 2021

Mendelian randomization uses genetic variants as instrumental variables to make causal inferences about the effect of a risk factor on an outcome. If a genetic variant satisfies the instrumental variable assumptions for the given risk factor and outcome, then an association between the genetic variant and the outcome implies the risk factor affects the outcome in some individuals at some point in the life-course.

Combining the instrumental variable assumptions with further assumptions and precise specification of the outcome (including specifying a time period for the outcome) allows valid testing of a more specific causal hypothesis and/or valid estimation of global or local, and point or period average causal effects.

In this short manuscript, the researchers discuss three ways in which Mendelian randomization analyses may be susceptible to bias due to reverse causation. They conclude that while the analyses offer some protection against biases, they are not totally immune from the phenomenon; and that researchers should consider carefully whether their findings could be explained by genetic variants having a primary association with the outcome, and how previous versions of an outcome can impact the stated risk factor.

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Publication: Stroke AHA

Eric L. Harshfield, Marios K. Georgakis, Rainer Malik, Martin Dichgans, Hugh S. Markus

4 February 2021

Summary

Assessing whether modifiable risk factors are causally associated with stroke risk is important in planning public health measures, but determining causality can be difficult in epidemiological data.

Here the research team evaluated whether modifiable lifestyle factors including educational attainment, smoking, and body mass index are causal risk factors for ischemic stroke and its subtypes and hemorrhagic stroke.

They performed 2-sample and multivariable Mendelian randomization to assess the causal effect of 12 lifestyle factors on risk of stroke and whether these effects are independent.

Genetically predicted years of education was inversely associated with ischemic, large artery, and small vessel stroke, and intracerebral hemorrhage.

Genetically predicted smoking, body mass index, and waist-hip ratio were associated with ischemic and large artery stroke. The effects of education, body mass index, and smoking on ischemic stroke were independent.

These findings support the hypothesis that reduced education and increased smoking and obesity increase risk of ischemic, large artery, and small vessel stroke, suggesting that lifestyle modifications addressing these risk factors will reduce stroke risk.

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Publication: Transfusion Medicine

Steven Bell, Michael Sweeting, Anna Ramond, Ryan Chung, Stephen Kaptoge, Matthew Walker, Thomas Bolton, Jennifer Sambrook, Carmel Moore, Amy McMahon, Sarah Fahle

20 December 2020

To safeguard donors, blood services measure haemoglobin concentration in advance of each donation. NHS Blood and Transplant’s (NHSBT) customary method have been capillary gravimetry (copper sulphate), followed by venous spectrophotometry (HemoCue) for donors failing gravimetry. However, NHSBT’s customary method results in 10% of donors being inappropriately bled (ie, with haemoglobin values below the regulatory threshold).

Here the researchers compared the following four methods in 21 840 blood donors (aged ≥18 years) recruited from 10 NHSBT centres in England, with the Sysmex XN‐2000 haematology analyser, the reference standard: (1) NHSBT’s customary method; (2) “post donation” approach, that is, estimating current haemoglobin concentration from that measured by a haematology analyser at a donor’s most recent prior donation; (3) “portable haemoglobinometry” (using capillary HemoCue); (4) non‐invasive spectrometry (using MBR Haemospect or Orsense NMB200). The team assessed sensitivity; specificity; proportion who would have been inappropriately bled, or rejected from donation (“deferred”) incorrectly; and test preference.

Compared with the reference standard, the methods ranged in test sensitivity from 17.0% (MBR Haemospect) to 79.0% (portable haemoglobinometry) in men, and from 19.0% (MBR Haemospect) to 82.8% (portable haemoglobinometry) in women.

For specificity, the methods ranged from 87.2% (MBR Haemospect) to 99.9% (NHSBT’s customary method) in men, and from 74.1% (Orsense NMB200) to 99.8% (NHSBT’s customary method) in women. The proportion of donors who would have been inappropriately bled ranged from 2.2% in men for portable haemoglobinometry to 18.9% in women for MBR Haemospect. The proportion of donors who would have been deferred incorrectly with haemoglobin concentration above the minimum threshold ranged from 0.1% in men for NHSBT’s customary method to 20.3% in women for OrSense. Most donors preferred non‐invasive spectrometry.

In the largest study reporting head‐to‐head comparisons of four methods to measure haemoglobin prior to blood donation, the results support replacement of NHSBT’s customary method with portable haemoglobinometry.

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