TY - JOUR

T1 - Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence

T2 - results from a collaborative meta-analysis

AU - Hartwig, Fernando Pires

AU - Davies, Neil Martin

AU - Horta, Bernardo Lessa

AU - Ahluwalia, Tarunveer S

AU - Bisgaard, Hans

AU - Bønnelykke, Klaus

AU - Caspi, Avshalom

AU - Moffitt, Terrie E

AU - Poulton, Richie

AU - Sajjad, Ayesha

AU - Tiemeier, Henning W

AU - Dalmau-Bueno, Albert

AU - Guxens, Mònica

AU - Bustamante, Mariona

AU - Santa-Marina, Loreto

AU - Parker, Nadine

AU - Paus, Tomáš

AU - Pausova, Zdenka

AU - Lauritzen, Lotte

AU - Schnurr, Theresia Maria

AU - Michaelsen, Kim F.

AU - Hansen, Torben

AU - Oddy, Wendy

AU - Pennell, Craig E

AU - Warrington, Nicole M

AU - Davey Smith, George

AU - Victora, Cesar Gomes

N1 - CURIS 2019 NEXS 074

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Faculty of Science

KW - Breastfeeding

KW - Intelligence

KW - FADS2

KW - Fatty acids

KW - Effect modification

KW - Meta-analysis

U2 - 10.1093/ije/dyy273

DO - 10.1093/ije/dyy273

M3 - Journal article

C2 - 30541029

VL - 48

SP - 45

EP - 57

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

SN - 0300-5771

IS - 1

ER -