X chromosome association analyses using multiple models identifies 18 genetic loci influencing dietary intake in UK Biobank

), including 17 variants without prior associations in the GWAS Catalog. Among these loci, 10 were significant across multiple X-WAS models, and 5 were strongest in a model other than the traditional sex-combined additive GWAS, highlighting the value of approaches that address known complexities of the X chromosome. These results demonstrate that incorporating the X chromosome in GWAS can reveal novel loci, even for complex behavioral traits such as dietary intake. Applying multiple association models further improves discovery by accounting for unique features of the X chromosome. Author Summary: Although diet is a major risk factor for many common diseases, adherence to healthy eating guidelines remains low. One reason is that current recommendations do not account for individual differences in food choice that arise from environmental or genetic factors. Previous genetic studies have identified hundreds of genetic variants associated with dietary behaviors, but most have excluded the X chromosome due to its analytical complexity and differences between males and females. However, accumulating evidence suggests that the X chromosome contains important genetic variation that impacts complex traits.We analyzed data from hundreds of thousands of individuals to identify genetic variants on the X chromosome associated with dietary intake. To address the unique features of the X chromosome, we applied multiple different models that account for sex-differences and non-additive genetic effects. We identified 18 regions in the genome associated with at least one dietary intake trait. These results reveal new insights into the genetics underlying eating behavior and highlight the importance of incorporating the X chromosome in genetic studies of complex traits.