Irfan Khan

Measuring a person’s waist-to-hip ratio (WHR) – particularly genetically determined WHR – has a stronger association with illness and death than either body mass index (BMI) or fat mass index (FMI), a group of genetic researchers at PHRI’s CRLB-GMEL lab.

The result for patients could be more precise recommendations around body shape (fat distribution) to affect a drop in disease burden and all-cause mortality in obese people.

“WHR better reflects levels of abdominal fat, including visceral fat, which wraps around the organs deep inside the body and raises the risk of a range of conditions, including type 2 diabetes and heart disease,” says Irfan Khan, a medical student at University College Cork, Ireland and formerly at CRLB-GMEL.

He presented an abstract on the research at the 8th annual meeting of the European Association for the Study of Diabetes (EASD) in Stockholm, Sweden this week.

CRLB-GMEL laboratory management team

Paré and Chong

Genetic variants can change the risk of disease

Khan’s study teammates include his mentor, Guillaume Paré , PHRI Senior Scientist and Director, CRLB-GMEL, Michael Chong, Assistant Director of the lab, among others. Paré notes:

We need additional tools to understand relationships between adiposity and health outcomes.
This is where genetics comes in handy. For example, we know that certain diseases lead to weight loss and also increase the risk of death.
When looking at this relationship, one might be tempted to conclude that lower weight causes increased risk of death. However, this is likely not the case.
Genetic associations are immune to this type of bias, called reverse causation. Diseases do not change genetic variants, but genetic variants can change the risk of disease.

The researchers looked at populations in the UK Biobank, with a discovery cohort used to derive genetically-determined adiposity measures. Observational relationships between BMI, WHR, and FMI with mortality from all-cause, cancer, cardiovascular disease (CVD), respiratory disease, or non-CVD, were analysed and then assessed with Mendelian randomization.

The study population consisted of 25,297 deaths and 25,297 randomly selected Caucasian age- and sex-matched controls from the UK Biobank, with average age of 61 59.3% male.

Ethnicity and sex variability

“While our results need to be replicated in individuals of diverse genetic ancestry, they also suggest that lower WHR is better, irrespective of setting,” says Khan. “This is a further advantage over BMI where ethnicity is more likely to impact the optimal BMI, defined as the BMI associated with lowest mortality.

In that regard, recommending the same target BMI across all populations is likely not ideal as we already know the optimal BMI varies from one population to the other,” Khan adds.

Genetically-determined WHR had a stronger association with all-cause mortality compared to BMI or FMI – regardless of the levels of adiposity and body composition – and exhibited a stronger effect in males compared to females. The researchers suggest that clinical recommendations and interventions should prioritize setting healthy WHR targets for males and females – rather than general BMI targets.

Sept. 20, EASD 2022, Stockholm: Medical student Irfan Khan presents on research out of the CRLB-GMEL lab at PHRI/Hamilton Health Sciences showing the limitations of BMI as a measure of assessing health risks in people with obesity.

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