OBJECTIVE

We tested whether genetic variants near fatty acid desaturases gene () cluster, which were recently identified to be signatures of adaptation to fish-rich and n-3 polyunsaturated fatty acids (PUFAs)-rich diet, interacted with these dietary factors on change in body mass index (BMI).

DESIGN

Three variants were examined for gene-diet interactions on long-term (~10 years) changes in BMI and body weight in four prospective cohort studies.

SETTING

Population based study.

PARTICIPANTS

11 323 women from the Nurses' Health Study (NHS), 6833 men from the Health Professionals Follow-up Study (HPFS) and replicated in 6254 women from the Women's Health Initiative (WHI) and 5 264 Chinese from the Singapore Chinese Health Study (SCHS).

MAIN OUTCOMES

Long-term (~10 years) changes in BMI and body weight.

RESULTS

In the NHS and HPFS cohorts, food-sourced n-3 PUFAs intake showed interactions with the rs174570 on changes of BMI (P for interaction=0.02 in NHS, 0.05 in HPFS and 0.007 in combined). Such interactions were replicated in two independent cohorts WHI and SCHS (P for interaction=0.04 in WHI, 0.02 in SCHS and 0.001 in combined). The genetic associations of the rs174570 with changes in BMI increased across the tertiles of n-3 PUFAs in all the cohorts. Fish intake also accentuated the genetic associations of the rs174570 with long-term changes in BMI (pooled P for interaction=0.006). Viewed differently, long chain n-3 PUFAs intake showed stronger association with long-term changes in BMI among the rs174570 T carriers (beta=0.79 kg/m per g, p=3×10) than the rs174570 non-T carriers (beta=0.16 kg/m per g, p=0.08). Similar results were observed for fish intake.

CONCLUSIONS

Our hypothesis-driven analyses provide replicable evidence that long chain n-3 PUFAs and fish intakes may interact with the variant on long-term weight gain. Further investigation is needed to confirm our findings in other cohorts.