Effect modification of <i>FADS2</i> polymorphisms on the association between breastfeeding and intelligence: results from a collaborative meta-analysis
Bibliographic record
Abstract
Abstract Background Accumulating evidence suggests that breastfeeding benefits the children’s intelligence. Long-chain polyunsaturated fatty acids (LC-PUFAs) present in breast milk may explain part of this association. 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 and Findings We investigated this Gene×Environment interaction in a de novo meta-analysis involving >12,000 individuals in the primary analysis, and >45,000 individuals in a secondary analysis using relaxed inclusion criteria. Our primary analysis used ever breastfeeding, FADS2 polymorphisms rs174575 and rs1535 coded assuming a recessive effect of the G allele, and intelligence quotient (IQ) in Z scores. Using random effects meta-analysis, ever breastfeeding was associated with 0.17 (95% CI: 0.03; 0.32) higher Z scores in IQ, or about 2.1 points. There was no strong evidence of interaction, with pooled covariate-adjusted interaction coefficients (i.e., difference between genetic groups of the difference in IQZ scores comparing ever with never breastfed individuals) of 0.12 (95% 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. However, between-group comparisons were underpowered. Conclusions Our findings do not support an interaction between ever breastfeeding and FADS2 polymorphisms. However, our subgroup analysis raises the possibility that breastfeeding supplies LC-PUFAs requirements for cognitive development (if such threshold exists) if it lasts for some (currently unknown) time. Future studies in large individual-level datasets would allow properly powered subgroup analyses and would improve our understanding on the role of breastfeeding duration in the breastfeeding× FADS2 interaction.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.021 | 0.044 |
| Meta-epidemiology (narrow) | 0.004 | 0.002 |
| Meta-epidemiology (broad) | 0.017 | 0.074 |
| Bibliometrics | 0.003 | 0.004 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.001 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.003 | 0.004 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".