This study conducted genome-wide association meta-analyses to identify genetic loci associated with body fat distribution, specifically waist-to-hip ratio (WHR) adjusted for body mass index (WHRadjBMI). The analysis included up to 224,459 individuals from various cohorts, combining data from genome-wide SNP arrays and the Metabochip. The researchers identified 49 new loci associated with WHRadjBMI, 33 of which were novel. These loci showed significant sexual dimorphism, with 20 out of 49 showing stronger effects in women. The identified loci were enriched for genes expressed in adipose tissue and regulatory elements in adipocytes. Pathway analyses highlighted adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as key processes affecting fat distribution. The study also explored the genetic architecture of WHRadjBMI, revealing a larger heritability in women compared to men. Additionally, the researchers evaluated the association of WHRadjBMI variants with other cardiometabolic traits and identified multiple association signals within observed loci. The findings provide insights into the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, emphasizing the importance of adipose tissue in these processes.This study conducted genome-wide association meta-analyses to identify genetic loci associated with body fat distribution, specifically waist-to-hip ratio (WHR) adjusted for body mass index (WHRadjBMI). The analysis included up to 224,459 individuals from various cohorts, combining data from genome-wide SNP arrays and the Metabochip. The researchers identified 49 new loci associated with WHRadjBMI, 33 of which were novel. These loci showed significant sexual dimorphism, with 20 out of 49 showing stronger effects in women. The identified loci were enriched for genes expressed in adipose tissue and regulatory elements in adipocytes. Pathway analyses highlighted adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as key processes affecting fat distribution. The study also explored the genetic architecture of WHRadjBMI, revealing a larger heritability in women compared to men. Additionally, the researchers evaluated the association of WHRadjBMI variants with other cardiometabolic traits and identified multiple association signals within observed loci. The findings provide insights into the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, emphasizing the importance of adipose tissue in these processes.