Maternal FADS2 single nucleotide polymorphism modified the impact of prenatal docosahexaenoic acid (DHA) supplementation on child neurodevelopment at 5 years: Follow-up of a randomized clinical trial

González-Casanova, Inés; Schoen, Meriah; Tandon, Sonia; Stein, Aryeh D.; Villarreal, Albino Barraza; DiGirolamo, Ann; Demmelmair, Hans; Silva, Ivonne Ramírez; Feregrino, Raquel Garcia; Rzehak, Peter; Stevenson, India; Standl, Marie; Schnaas, Lourdes; Romieu, Isabelle; Koletzko, Berthold; Ramakrishnan, Usha

doi:10.1016/j.clnu.2021.08.026

Cited by 10 publications

(4 citation statements)

References 31 publications

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“…In an RCT conducted in Mexico, 1094 women received 400 mg/d of algal DHA from 18 or 22 weeks of gestation until delivery to explore the beneficial effects on mothers and offspring from delivery until 5 years of age (ClinicalTrials.gov ID: NCT00646360) [229,230]. The emerging adverse events were not significantly different between the intervention and control groups, and were not related with algal oil intake.…”

Section: Microalgaementioning

confidence: 99%

Promising Sources of Plant-Derived Polyunsaturated Fatty Acids: A Narrative Review

Rizzo¹,

Baroni²,

Lombardo³

2023

IJERPH

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(1) Background: Polyunsaturated fatty acids (PUFAs) are known for their ability to protect against numerous metabolic disorders. The consumption of oily fish is the main source of PUFAs in human nutrition and is commonly used for supplement production. However, seafood is an overexploited source that cannot be guaranteed to cover the global demands. Furthermore, it is not consumed by everyone for ecological, economic, ethical, geographical and taste reasons. The growing demand for natural dietary sources of PUFAs suggests that current nutritional sources are insufficient to meet global needs, and less and less will be. Therefore, it is crucial to find sustainable sources that are acceptable to all, meeting the world population’s needs. (2) Scope: This review aims to evaluate the recent evidence about alternative plant sources of essential fatty acids, focusing on long-chain omega-3 (n-3) PUFAs. (3) Method: A structured search was performed on the PubMed search engine to select available human data from interventional studies using omega-3 fatty acids of non-animal origin. (4) Results: Several promising sources have emerged from the literature, such as algae, microorganisms, plants rich in stearidonic acid and GM plants. However, the costs, acceptance and adequate formulation deserve further investigation.

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Section: Microalgaementioning

confidence: 99%

Promising Sources of Plant-Derived Polyunsaturated Fatty Acids: A Narrative Review

Rizzo¹,

Baroni²,

Lombardo³

2023

IJERPH

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“…As a natural extension, we investigated the impact of FADS1 and FADS2 gene expression on cognitive function. The FADS variants have been reported to be associated with cognitive function in previous studies, but the association has only been studied in the context of the effect of FADS gene variation on children or offspring [50][51][52][53]. Genetic variants in the FADS1/FADS2 region are associated with maternal long-chain polyunsaturated fatty acid status and could modified cognitive development of infants [50].…”

Section: Discussionmentioning

confidence: 99%

“…The FADS variants have been reported to be associated with cognitive function in previous studies, but the association has only been studied in the context of the effect of FADS gene variation on children or offspring [50][51][52][53]. Genetic variants in the FADS1/FADS2 region are associated with maternal long-chain polyunsaturated fatty acid status and could modified cognitive development of infants [50]. In addition, FADS1/ FADS2 genetic variants have been reported to be associated with behavioral outcomes in children [52,53].…”

Section: Discussionmentioning

confidence: 99%

Brain tissue- and cell type-specific eQTL Mendelian randomization reveals efficacy of FADS1 and FADS2 on cognitive function

Wu,

Jiang,

et al. 2024

Transl Psychiatry

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Epidemiological studies suggested an association between omega-3 fatty acids and cognitive function. However, the causal role of the fatty acid desaturase (FADS) gene, which play a key role in regulating omega-3 fatty acids biosynthesis, on cognitive function is unclear. Hence, we used two-sample Mendelian randomization (MR) to estimate the gene-specific causal effect of omega-3 fatty acids (N = 114,999) on cognitive function (N = 300,486). Tissue- and cell type-specific effects of FADS1/FADS2 expression on cognitive function were estimated using brain tissue cis-expression quantitative trait loci (cis-eQTL) datasets (GTEx, N ≤ 209; MetaBrain, N ≤ 8,613) and single cell cis-eQTL data (N = 373), respectively. These causal effects were further evaluated in whole blood cis-eQTL data (N ≤ 31,684). A series of sensitivity analyses were conducted to validate MR assumptions. Leave-one-out MR showed a FADS gene-specific effect of omega-3 fatty acids on cognitive function [β = −1.3 × 10−2, 95% confidence interval (CI) (−2.2 × 10−2, −5 × 10−3), P = 2 × 10−3]. Tissue-specific MR showed an effect of increased FADS1 expression in cerebellar hemisphere and FADS2 expression in nucleus accumbens basal ganglia on maintaining cognitive function, while decreased FADS1 expression in nine brain tissues on maintaining cognitive function [colocalization probability (PP.H4) ranged from 71.7% to 100.0%]. Cell type-specific MR showed decreased FADS1/FADS2 expression in oligodendrocyte was associated with maintaining cognitive function (PP.H4 = 82.3%, respectively). Increased FADS1/FADS2 expression in whole blood showed an effect on cognitive function maintenance (PP.H4 = 86.6% and 88.4%, respectively). This study revealed putative causal effect of FADS1/FADS2 expression in brain tissues and blood on cognitive function. These findings provided evidence to prioritize FADS gene as potential target gene for maintenance of cognitive function.

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“…FADS2 codifies enzymes present in the endoplasmic reticulum and mitochondria responsible the insertion of double bonds in fatty acid molecules, primarily on the 6 th carbon-carbon bond (Δ6 desaturase). This step is common to the metabolic pathway of both n-3 and n-6 fatty acids (41)(42)(43) and polymorphisms in FADS2 associate with different levels of DHA and AA in serum and breastmilk (12,42,(44)(45)(46)(47)(48).…”

Section: Introductionmentioning

confidence: 99%

No evidence of interaction betweenFADS2genotype and breastfeeding on cognitive or other traits in the UK Biobank

Centorame,

Warrington,

Hemani

et al. 2024

Preprint

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BackgroundBreastfeeding is hypothesised to benefit child health and cognitive functioning by providing long-chain polyunsaturated fatty acids (LC-PUFA), which are essential for brain development. In 2007, Caspiet al.found evidence in two cohorts for an interaction between genetic variation in theFADS2gene (a gene involved in fatty acid metabolism) and breast feeding on IQ. However, subsequent studies have provided mixed evidence for the existence of an interaction.ObjectiveTo investigate the relationship between genetic variation in theFADS2region, breastfeeding, and their interaction on traits putatively affected by their interplay in a large, population-based cohort with appropriate control for confounders in genetic associations.MethodsWe tested for the interaction in up to 335,650 individuals from the UK Biobank, over a range of cognitive functioning tests, as well as educational attainment and other traits thought to be influenced by breastfeeding, including cardiometabolic traits, reproductive success, and atopic allergy.ResultsFADS2alleles associated with an increase in docosahexaenoic acid (DHA) in blood serum (the C allele of rs174575) were associated with decreased verbal-numerical reasoning (p=2.28× 10−5) and triglycerides (p=1. 40× 10−41), increased reproductive success (p=3. 40× 10−5), total cholesterol (p=5. 28× 10−36), HDL (p=1. 42× 10− 51), and LDL cholesterol (p=1. 46× 10− 21). We observed no evidence of an interaction in any of the traits, regardless of the modelling strategy.ConclusionsWe failed to replicate any breastfeeding by genotype interactions on any cognitive or non-cognitive traits. We postulate that the previous positive findings are likely to be spurious, perhaps due to lack of appropriate control for latent population structure.

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Maternal FADS2 single nucleotide polymorphism modified the impact of prenatal docosahexaenoic acid (DHA) supplementation on child neurodevelopment at 5 years: Follow-up of a randomized clinical trial

Cited by 10 publications

References 31 publications

Promising Sources of Plant-Derived Polyunsaturated Fatty Acids: A Narrative Review

Promising Sources of Plant-Derived Polyunsaturated Fatty Acids: A Narrative Review

Brain tissue- and cell type-specific eQTL Mendelian randomization reveals efficacy of FADS1 and FADS2 on cognitive function

No evidence of interaction betweenFADS2genotype and breastfeeding on cognitive or other traits in the UK Biobank

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