The secret to how your body handles dangerous trans fats may be written in your DNA.
Have you ever wondered why two people can follow similar diets yet experience dramatically different health outcomes? The answer may lie not just on our plates, but in our genetic blueprint. For years, scientists have understood that trans fatty acids—artificial fats found in partially hydrogenated oils—significantly increase the risk of heart disease, diabetes, and inflammation. What has remained mysterious is why these dangerous fats persist at different levels in different people's bloodstreams, even when they consume similar amounts.
Groundbreaking research from an international scientific collaboration has now uncovered a crucial piece of this puzzle, revealing that our genes play a surprising role in how our bodies handle these harmful fats. The discovery opens new pathways for understanding the complex interplay between nutrition and genetics, potentially paving the way for more personalized dietary recommendations in the future.
Study Participants
Genetic Variations Identified
Major Studies Combined
To tackle the mystery of circulating trans fats, researchers needed data on a scale no single institution could provide. Enter the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, an international alliance of population-based studies that pools genetic and health data from tens of thousands of participants across multiple countries.
The Consortium performed a meta-analysis of genome-wide association studies (GWAS) combining results from multiple genetic studies to enhance statistical power.
"The funders had no role in the design, implementation, analysis, or interpretation of the data" - Dr. Dariush Mozaffarian, senior researcher 1
The Consortium's meta-analysis yielded a striking discovery: variations in a specific genetic region known as the fatty acid desaturase (FADS) gene cluster significantly influence how our bodies process a particular type of trans fat. This region on chromosome 11 contains genes that code for enzymes called desaturases, which play crucial roles in converting dietary fats into various forms the body can use 2 .
Researchers found that 31 different genetic variations in and near the FADS1 and FADS2 genes were associated with levels of cis/trans-18:2—a specific form of trans fatty acid found in circulation.
The strongest association was with a genetic variant known as rs174548 in the FADS1 gene. Each copy of the effect allele at this location was associated with increased cis/trans-18:2 levels 2 .
| Genetic Element | Association | Population | Effect Size | P-value |
|---|---|---|---|---|
| rs174548 in FADS1 | cis/trans-18:2 | European-ancestry | β = 0.0035 | 4.90 × 10-15 |
| rs174548 in FADS1 | cis/trans-18:2 | Hispanic Americans | β = 0.0053 | 1.05 × 10-6 |
| rs174548 in FADS1 | cis/trans-18:2 | Chinese Americans | β = 0.0028 | 0.002 |
| rs174579 in FADS2 | cis/trans-18:2 | African Americans | β = 0.0118 | 4.05 × 10-5 |
Table 1: Key Genetic Findings from the CHARGE Consortium Meta-Analysis 2
Perhaps the most fascinating insight came when researchers discovered that the association between the FADS genetic variant and cis/trans-18:2 was dramatically reduced—by 86% in European-ancestry participants—when they statistically adjusted for levels of arachidonic acid, an omega-6 polyunsaturated fat 2 . This suggests that the genetic effect on trans fats may be mediated through its influence on arachidonic acid.
How exactly did researchers identify these tiny genetic needles in the enormous haystack of human DNA? The CHARGE Consortium employed a sophisticated multi-step approach that combined cutting-edge genetic technology with rigorous statistical analysis.
Each participating cohort conducted their own genome-wide association study. Participants provided blood samples for genetic analysis and measurement of circulating fatty acid levels in either erythrocyte membranes or plasma phospholipids 1 2 .
Researchers used high-density single nucleotide polymorphism (SNP) arrays that scan hundreds of thousands of genetic markers across the genome. Different platforms were used across studies, including Affymetrix 6.0 and various Illumina arrays 2 .
To fill in gaps between directly genotyped markers, researchers used imputation techniques that statistically infer missing genotypes based on reference panels like HapMap, resulting in approximately 2.5 million genetic variants tested per participant 2 .
Within each cohort, researchers examined associations between each genetic variant and five different trans fatty acids. Each analysis adjusted for potential confounding factors like age, sex, and population substructure 2 .
Study-specific results were combined through a meta-analysis using specialized software that weighted each study's contribution according to its sample size and precision 2 .
| Study Name | Participants | Fatty Acid Measurement | Genotyping Platform |
|---|---|---|---|
| CARDIA | Young adults | Plasma phospholipids | Affymetrix 6.0 |
| CHS | Older adults | Plasma phospholipids | Illumina 370 |
| GOLDN | Families | Erythrocyte membranes | Affymetrix 6.0 |
| HPFS | Male health professionals | Erythrocyte membranes | Illumina 550K-610Q |
| NHS | Female nurses | Erythrocyte membranes | Illumina 550K-610Q |
| MESA | Multi-ethnic adults | Plasma phospholipids | Affymetrix 6.0 |
Table 2: Participating Studies in the CHARGE Consortium Meta-Analysis 2
The discovery of genetic variants influencing circulating trans fatty acid levels represents more than just a scientific curiosity—it opens new avenues for understanding human nutrition and disease prevention.
The findings help explain why dietary biomarkers like circulating trans fats may only modestly correlate with self-reported consumption 5 .
The mediating role of arachidonic acid suggests intriguing biological mechanisms worth exploring further 2 .
Looking ahead, this research could eventually contribute to more personalized nutrition recommendations. While the current findings don't yet support genetic testing for trans fat metabolism, they represent an important step toward understanding how individual genetic differences affect our responses to dietary fats.
As one subsequent study in Nature noted, "Large genome-wide association studies coupled with metabolic profiling platforms have successfully identified many loci associated with circulating metabolic traits" 7 , highlighting how this type of research is part of a broader scientific movement to understand the genetic architecture of human metabolism.
In the meantime, the public health message on trans fats remains clear: minimizing consumption is one of the most straightforward ways to support cardiovascular health. But thanks to this groundbreaking genetic research, we now have a deeper appreciation of the complex biological processes that determine what happens after these fats enter our bodies.