Gene linked to growth hormone affects obesity risk differently in men and women
A UK study of 500,000+ people found that variants in the LEAP2 gene influence body weight and fat distribution, with stronger effects in women. The discovery could open new avenues for personalized obesity treatments and reshape how pharmaceutical companies approach weight-management drug development across sexes.
Originaltitel: Genetic variants of <em>LEAP2</em> are associated with anthropometric traits and circulating insulin-like growth factor-1 concentration: A UK Biobank study
<p>Aim: To test the hypothesis that liver-expressed antimicrobial peptide 2 (LEAP2) genetic variants might influence the susceptibility to human obesity.</p><p>Methods: Using data from the UK Biobank, we identified independent LEAP2 gene single nucleotide polymorphisms (SNPs) and examined their associations with obesity traits and serum insulin-like growth factor-1 (IGF-1) concentration. These associations were evaluated for both individual SNPs and after combining them into a genetic risk score (GRSLEAP2) using linear and logistic regression models. Sex-stratified analyses were also conducted.</p><p>Results: Five SNPs showed positive associations with obesity-related traits. rs57880964 was associated with body mass index (BMI) and waist-to-hip ratio adjusted for BMI (WHRadjBMI), in the total population and among women. Four independent SNPs were positively associated with higher serum IGF-1 concentrations in both men and women. GRSLEAP2 was associated with BMI and WHRadjBMI only in women and with serum IGF-1 concentration in both sexes.</p><p>Conclusions: These findings reveal sex-specific associations between key LEAP2 gene variants and several obesity traits, while also indicating a strong independent association of LEAP2 variants with serum IGF-1 concentration.</p>