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

Journal: International journal of epidemiology 2020;48(1):45-57

PMID: 30541029

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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 <5.85 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.

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

DOI: 10.1093/ije/dyy273

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MeSH Terms: Breast Feeding, Cognition, Fatty Acid Desaturases, Female, Genotype, Humans, Intelligence, Intelligence Tests, Linear Models, Male, Polymorphism, Genetic