X chromosome study reveals new genetic links to dietary intake

Genetic variants on the X chromosome are linked to what people eat, according to a new X-chromosome-wide association study published in Genes & Nutrition. Researchers identified 18 loci associated with 20 dietary traits, several of which had not previously been tied to dietary intake, and showed that models accounting for sex-specific effects can uncover associations that conventional analyses miss.

The study, led by Maizy S. Brasher-Harju and colleagues with senior author Joanne B. Cole, addressed a long-standing gap in nutritional genetics. Genome-wide association studies have identified hundreds of loci associated with dietary intake, but the X chromosome, a major source of sex-linked genetic variation, has largely been excluded from these scans. Because adherence to dietary recommendations remains low and may reflect individual differences in intake arising from environmental and genetic factors, the team set out to test whether X-linked variants contribute to eating behavior.

The analysis drew on 46 dietary intake traits collected through food frequency questionnaires from 424,758 participants of European ancestry in the UK Biobank. The phenotypes included quantitative measures such as fruit intake, binary traits such as choosing decaffeinated versus caffeinated coffee, and principal component-derived food groups. Rather than applying a single statistical model, the researchers tested five X-WAS approaches: a traditional sex-combined additive model, sex-stratified additive models, a joint model that accounts for sex interactions, and a model for non-additive genetic effects.

The scan produced associations at 18 loci reaching the conventional genome-wide significance threshold of P<5 × 10−8. Two of these loci, GPR173 and HTR2C, had prior evidence of biological mechanisms related to dietary behavior. Five loci showed stronger associations in models that accounted for sex-specific effects, and one locus, marked by the variant rs191475305, showed a significant SNP-by-sex interaction in relation to meat intake, underscoring the importance of considering the unique biology of the X chromosome.

To test how robust the findings were, the team assessed generalizability across six ancestry groups within the UK Biobank and conducted a multi-ancestry meta-analysis of 445,773 participants. Eight of the nine loci tested showed consistent effects across ancestry groups, with heterogeneity P values above 0.05. The researchers also sought replication of female-specific findings in the Women’s Genome Health Study, a cohort of 23,129 women, where two of six loci replicated at P<0.05.

Beyond the primary scan, the authors performed phenome-wide association studies and covariate sensitivity analyses of known confounders of diet to characterize the biological context of the associated loci. These checks are intended to help distinguish genuine dietary associations from effects that might arise through related traits or confounding factors.

The overall conclusion, according to the authors, is that most associations were detectable using conventional sex-combined analyses, but models accounting for sex-specific and non-additive effects produced the strongest associations on several occasions. The findings establish the X chromosome as a component of the genetic architecture of dietary intake and demonstrate the value of purpose-built X-chromosome models for genetic discovery.

The article, published on 15 October 2026 as an open-access research paper, is being shared early to provide faster access to peer-reviewed, accepted research; the version is subject to further edits and will be replaced by the final Version of Record. As with any association study, the reported loci indicate statistical links between genetic variants and reported dietary intake in the populations studied, and the replication rate in the external female cohort was partial, with two of six loci replicating.

Subject of Research: X-chromosome-wide association study of genetic variants linked to dietary intake

Article Title: Comprehensive X-chromosome association analysis identifies novel genetic associations with dietary intake

Article References: Brasher-Harju, M. S., Sutton, K. J., Patterson, W. B., Giulianini, F., Chasman, D. I., & Cole, J. B. (2026). Comprehensive X-chromosome association analysis identifies novel genetic associations with dietary intake. Genes & Nutrition. https://doi.org/10.1186/s12263-026-00823-x

Image Credits: AI Generated

DOI: 10.1186/s12263-026-00823-x

Keywords: X chromosome, dietary intake, GWAS, UK Biobank, genetics, nutrition, sex differences, food preference, association study, genetic loci, Comprehensive, X-chromosome