Genetics identifies obesity as a shared risk factor for co-occurring multiple long-term conditions.

Area of Science:

• Genetics and Public Health

Background:

• Multimorbidity, the co-occurrence of multiple long-term conditions (LTCs), is a growing health concern.
• The genetic underpinnings of multimorbidity are not well understood.
• Obesity, indicated by body mass index (BMI), is a potential key risk factor.

Purpose of the Study:

• To investigate the role of BMI genetics in explaining shared genetic factors among 71 common LTCs.
• To determine if BMI causally influences individual LTCs and their co-occurrence.
• To quantify the potential impact of BMI reduction on multimorbidity prevalence.

Main Methods:

• Estimated genetic correlations between LTCs, with and without adjustment for BMI genetics, in a Northern European population.
• Employed multiple causal inference methods to establish BMI's causal effect on LTCs and their co-occurrence.
• Quantified the population-level effect of BMI reduction on 15 common multimorbid LTC pairs.

Main Results:

• BMI genetics partially explained shared genetics for 740 LTC pairs (30% of those studied).
• For 161 LTC pairs, shared genetics were entirely explained by BMI genetics, including conditions like diabetes and osteoarthritis.
• Causal inference confirmed BMI as a common risk factor for specific LTC pairs, suggesting BMI-lowering interventions could decrease their prevalence.

Conclusions:

• A genetics-centered approach effectively quantifies obesity's contribution to multimorbidity.
• The study provides a novel method for calculating genetic correlations, available as an R package {partialLDSC}.