Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence: results from a collaborative meta-analysis.
Background:Accumulating evidence suggests that breastfeeding benefits children's intelligence, possibly due to long-chain polyunsaturated fatty acids (LC-PUFAs) present in breast milk. Under a nutritional adequacy hypothesis, an interaction between breastfeeding and genetic variants associated with endogenous LC-PUFAs synthesis might be expected. However, the literature on this topic is controversial. Methods:We investigated this gene × environment interaction through a collaborative effort. The primary analysis involved >12 000 individuals and used ever breastfeeding, FADS2 polymorphisms rs174575 and rs1535 coded assuming a recessive effect of the G allele, and intelligence quotient (IQ) in Z scores. Results:There was no strong evidence of interaction, with pooled covariate-adjusted interaction coefficients (i.e. difference between genetic groups of the difference in IQ Z scores comparing ever with never breastfed individuals) of 0.12[(95% confidence interval (CI): -0.19; 0.43] and 0.06 (95% CI: -0.16; 0.27) for the rs174575 and rs1535 variants, respectively. Secondary analyses corroborated these results. In studies with ≥5.85 and <5.85 months of breastfeeding duration, pooled estimates for the rs174575 variant were 0.50 (95% CI: -0.06; 1.06) and 0.14 (95% CI: -0.10; 0.38), respectively, and 0.27 (95% CI: -0.28; 0.82) and -0.01 (95% CI: -0.19; 0.16) for the rs1535 variant. Conclusions:Our findings did not support an interaction between ever breastfeeding and FADS2 polymorphisms. However, subgroup analysis suggested that breastfeeding may supply LC-PUFAs requirements for cognitive development if breastfeeding lasts for some (currently unknown) time. Future studies in large individual-level datasets would allow properly powered subgroup analyses and further improve our understanding on the breastfeeding × FADS2 interaction.
Hartwig, FP; Davies, NM; Horta, BL; Ahluwalia, TS; Bisgaard, H; Bønnelykke, K; Caspi, A; Moffitt, TE; Poulton, R; Sajjad, A; Tiemeier, HW; Dalmau-Bueno, A; Guxens, M; Bustamante, M; Santa-Marina, L; Parker, N; Paus, T; Pausova, Z; Lauritzen, L; Schnurr, TM; Michaelsen, KF; Hansen, T; Oddy, W; Pennell, CE; Warrington, NM; Davey Smith, G; Victora, CG
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