Habitual consumption of long-chain n–3 PUFAs and fish attenuates genetically associated long-term weight gain

Abstract

ABSTRACT Background A growing amount of data suggests that n–3 (ω-3) polyunsaturated fatty acid (PUFA) intake may modify the genetic association with weight change. Objectives We aimed to prospectively test interactions of habitual consumption of n–3 PUFAs or fish, the major food source, with overall genetic susceptibility on long-term weight change. Design Gene–diet interactions were examined in 11,330 women from the Nurses’ Health Study (NHS), 6773 men from the Health Professionals Follow-Up Study (HPFS), and 6254 women from the Women's Health Initiative (WHI). Results In the NHS and HPFS cohorts, food-sourced long-chain n–3 PUFA intake showed directionally consistent interactions with genetic risk score on long-term changes in BMI (P-interaction = 0.01 in the HPFS, 0.15 in the NHS, and 0.01 in both cohorts combined). Such interactions were successfully replicated in the WHI, an independent cohort (P-interaction = 0.02 in the WHI and 0.01 in the combined 3 cohorts). The genetic associations with changes in BMI (in kg/m2) consistently decreased (0.15, 0.10, 0.07, and −0.14 per 10 BMI-increasing alleles) across the quartiles of long-chain n–3 PUFAs in the combined cohorts. In addition, high fish intake also attenuated the genetic associations with long-term changes in BMI in the HPFS (P-interaction = 0.01), NHS (P-interaction = 0.03), WHI (P-interaction = 0.10), and the combined cohorts (P-interaction = 0.01); and the differences in BMI changes per 10 BMI-increasing alleles were 0.16, 0.06, −0.08, and −0.18, respectively, across the categories (≤1, 1∼4, 4∼6, and ≥7 servings/wk) of total fish intake. Similar interactions on body weight were observed for fish intake (P-interaction = 0.003) and long-chain n–3 PUFA intake (P-interaction = 0.12). Conclusion Our study provides replicable evidence to show that high intakes of fish and long-chain n–3 PUFAs are associated with an attenuation of the genetic association with long-term weight gain based on results from 3 prospective cohorts of Caucasians.