Is your DNA steering you towards a vegetarian diet?

In a recent study published in PLoS ONE, researchers identified genetic loci associated with strict vegetarianism in United Kingdom Biobank (UKB) participants using a genome-wide association study (GWAS).

Study: Genetics of vegetarianism: A genome-wide association study. Image Credit: natalia bulatova / Shutterstock.com

Background 

Vegetarianism has been practiced for centuries by various religions, including Hinduism and Buddhism, as well as certain sects in ancient Greece. The health benefits of a vegetarian diet have been established; however, there are also concerns about potential nutritional deficiencies.

Despite its increasing popularity, only a tiny percentage of the global population practices strict vegetarianism. Interestingly, there appears to be a genetic aspect influencing dietary choices. Further research is needed to better understand how genetics may contribute to an individual’s ability to adopt and maintain a vegetarian lifestyle.

About the study

The current study utilized participant data from the UKB, a health research database that comprises about 500,000 individuals between 40-69 years of age. The UKB recorded data using physical examinations, sample collections, and detailed questionnaires, which included questions on dietary habits to identify vegetarians.

UKB operates with approval from the North West Multi-center Research Ethics Committee (MREC), thereby allowing researchers to use its data without seeking additional ethical clearance. All data are entirely anonymized, and all study participants initially provided electronic consent with the assurance that they could opt out at any time.

UKB performed genotyping and quality control on its ethnically diverse participants using the UK Biobank Lung Exome Variant Evaluation (UK BiLEVE) and UK Biobank Axiom Array (UKB Axio). Genotyped data were then pre-phased to determine individual haplotypes, followed by imputation using various reference panels. As a result, the imputed data consisted of over 93 million genetic markers.

Additional in-house quality controls were applied after receiving the data. From the initial pool, 161,655 samples were excluded due to various criteria, ultimately making 340,754 samples available for analysis. Genetic variants that did not meet specific quality criteria were also excluded, which led to 9,740,199 variants available for the study.

For phenotype processing, quality-controlled data were classified into vegetarians and non-vegetarians. Data for determining dietary habits were collected using two distinct questionnaires. Based on stringent screening criteria, 5,324 participants were identified as vegetarians and 329,455 as controls.

The study used Scalable and Accurate Implementation of a GEneralized mixed model (SAIGE) for genome-wide analysis, which considered factors like age and sex. Additional analyses utilized the Functional Mapping and Annotation platform (FUMA).

Study results 

In the present study, individuals defined as vegetarians were those who had not consumed animal flesh or products derived from it for at least one year. Their selection was based on data from the touchscreen questionnaire, which assessed diet over the past year and was completed by approximately 500,000 respondents on four occasions, as well as the 24-hour recall questionnaire, which detailed food intake from the previous day and was completed by about 110,000 participants five times.

Compared to controls, vegetarians were typically younger, female, had lower body mass indices and were from less affluent backgrounds. GWAS for vegetarianism exhibited mild inflation, possibly due to case-control imbalances, despite rigorous measures to ensure accurate analysis.

A gene-property analysis was executed to discern the specific tissues affected by the phenotype, highlighting the significance of 30 general tissue types. Several genes associated with vegetarianism were found to be particularly active in the brain. SNPs linked with vegetarianism were also associated with traits related to lipid metabolism and brain functioning.

One significant single nucleotide polymorphism (SNP) on chromosome 18 was identified. Several SNPs in the vicinity that were closely related to this SNP were also identified within genes like RIO kinase 3 (RIOK3), NPC intracellular cholesterol transporter 1 (NPC1), required for meiotic nuclear division 1 homolog (RMC1), and transmembrane protein 241 (TMEM241).

NPC1 was of particular interest, as it is linked with SNPs having the highest chance of being functionally significant. This gene plays a pivotal role in the internal movement of cholesterol and glycolipids.

Disruptions in NPC1 cause most Niemann-Pick disease type C cases, a condition marked by cholesterol accumulation in tissues that primarily causes neurological symptoms. These findings indicate that vegetarianism might have connections with lipid metabolism and its influence on brain activity. 

Taken together, there were 202 significant variants associated with 11 genes possibly influencing vegetarianism. Further scrutiny of the GWAS data using the FUMA platform led to the identification of 37 genomic risk locations for vegetarianism and linked 842 SNPs and 59 genes to those regions.