Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence: Results from a collaborative meta-analysis

Fernando Pires Hartwig*, Neil Martin Davies, Bernardo Lessa Horta, Tarunveer S Ahluwalia, Hans Bisgaard, Klaus Bønnelykke, Avshalom Caspi, Terrie E Moffitt, Richie Poulton, Ayesha Sajjad, Henning W Tiemeier, Albert Dalmau-Bueno, Mònica Guxens, Mariona Bustamante, Loreto Santa-Marina, Nadine Parker, Tomáš Paus, Zdenka Pausova, Lotte Lauritzen, Theresia M SchnurrKim F Michaelsen, Torben Hansen, Wendy Oddy, Craig E Pennell, Nicole M Warrington, George Davey Smith, Cesar Gomes Victora

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

2 Citations (Scopus)
299 Downloads (Pure)


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.

Original languageEnglish
Article numberdyy273
Pages (from-to)45-57
Number of pages13
JournalInternational Journal of Epidemiology
Issue number1
Early online date11 Dec 2018
Publication statusPublished - 1 Feb 2019


  • Breastfeeding
  • Intelligence
  • FADS2
  • Fatty acids
  • Effect modification
  • Meta-analysis


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