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Int J Epidemiol. 2019 Feb 1;48(1):45-57. doi: 10.1093/ije/dyy273.

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

Author information

1
Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
2
Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
3
Population Health Sciences, University of Bristol, Bristol, UK.
4
Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
5
Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.
6
Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
7
Department of Psychology, University of Otago, Dunedin, New Zealand.
8
Department of Epidemiology.
9
Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
10
ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
11
Department of Health and Life Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Spain.
12
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
13
Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain.
14
Basque Country Health Department, BIODONOSTIA Health Research Institute, San Sebastian, Spain.
15
Public Health Division of Gipuzkoa, BIODONOSTIA Health Research Institute, San Sebastian, Spain.
16
Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada.
17
Institute of Medical Science.
18
Departments of Psychiatry and Psychology, University of Toronto, Toronto, ON, Canada.
19
Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning, Toronto, ON, Canada.
20
Department of Nutritional Sciences.
21
Department of Physiology, University of Toronto, Toronto, ON, Canada.
22
Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.
23
Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Copenhagen, Denmark.
24
Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
25
School of Women's and Infants' Health, University of Western Australia, Perth, WA, Australia and.
26
University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.

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 <5.85 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.

KEYWORDS:

Breastfeeding; FADS2; effect modification; fatty acids; intelligence; meta-analysis

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