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 Maria Schnurr; Kim F. Michaelsen; Torben Hansen; Wendy Oddy; Craig E Pennell; Nicole M Warrington; George Davey Smith; Cesar Gomes Victora

doi:10.1093/ije/dyy273

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 Maria SchnurrKim F. Michaelsen, Torben Hansen, Wendy Oddy, Craig E Pennell, Nicole M Warrington, George Davey Smith, Cesar Gomes Victora

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Abstract

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 <5.85months 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 language	English
Journal	International Journal of Epidemiology
Volume	48
Issue number	1
Pages (from-to)	45-57
Number of pages	13
ISSN	0300-5771
DOIs	https://doi.org/10.1093/ije/dyy273
Publication status	Published - 1 Feb 2019

Keywords

Faculty of Science
Breastfeeding
Intelligence
FADS2
Fatty acids
Effect modification
Meta-analysis

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Hartwig et al_International Journal of Epidemiology_2019_Vol 48(1)_45-57Final published version, 765 KBLicence: CC BY

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Hartwig, F. P., Davies, N. M., Horta, B. L., Ahluwalia, T. S., Bisgaard, H., Bønnelykke, K., Caspi, A., Moffitt, T. E., Poulton, R., Sajjad, A., Tiemeier, H. W., Dalmau-Bueno, A., Guxens, M., Bustamante, M., Santa-Marina, L., Parker, N., Paus, T., Pausova, Z., Lauritzen, L., ... Victora, C. G. (2019). Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence: results from a collaborative meta-analysis. International Journal of Epidemiology, 48(1), 45-57. https://doi.org/10.1093/ije/dyy273

Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence : results from a collaborative meta-analysis. / Hartwig, Fernando Pires; Davies, Neil Martin; Horta, Bernardo Lessa et al.

In: International Journal of Epidemiology, Vol. 48, No. 1, 01.02.2019, p. 45-57.

Research output: Contribution to journal › Journal article › Research › peer-review

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 2019, 'Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence: results from a collaborative meta-analysis', International Journal of Epidemiology, vol. 48, no. 1, pp. 45-57. https://doi.org/10.1093/ije/dyy273

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title = "Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence: results from a collaborative meta-analysis",

abstract = "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 <5.85months 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.",

keywords = "Faculty of Science, Breastfeeding, Intelligence, FADS2, Fatty acids, Effect modification, Meta-analysis",

author = "Hartwig, {Fernando Pires} and Davies, {Neil Martin} and Horta, {Bernardo Lessa} and Ahluwalia, {Tarunveer S} and Hans Bisgaard and Klaus B{\o}nnelykke and Avshalom Caspi and Moffitt, {Terrie E} and Richie Poulton and Ayesha Sajjad and Tiemeier, {Henning W} and Albert Dalmau-Bueno and M{\`o}nica Guxens and Mariona Bustamante and Loreto Santa-Marina and Nadine Parker and Tom{\'a}{\v s} Paus and Zdenka Pausova and Lotte Lauritzen and Schnurr, {Theresia Maria} and Michaelsen, {Kim F.} and Torben Hansen and Wendy Oddy and Pennell, {Craig E} and Warrington, {Nicole M} and {Davey Smith}, George and Victora, {Cesar Gomes}",

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year = "2019",

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doi = "10.1093/ije/dyy273",

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volume = "48",

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journal = "International Journal of Epidemiology",

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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 - 2019/2/1

Y1 - 2019/2/1

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 <5.85months 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 <5.85months 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

SN - 0300-5771

VL - 48

SP - 45

EP - 57

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

IS - 1

ER -

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

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