July 16, 2010

Breastfeeding and IQ (Steer et al. 2010)

The new article references an older article by Caspi et al, which studied the moderation of the association between breastfeeding and IQ by a genetic variant in FADS2:
Children's intellectual development is influenced by both genetic inheritance and environmental experiences. Breastfeeding is one of the earliest such postnatal experiences. Breastfed children attain higher IQ scores than children not fed breast milk, presumably because of the fatty acids uniquely available in breast milk. Here we show that the association between breastfeeding and IQ is moderated by a genetic variant in FADS2, a gene involved in the genetic control of fatty acid pathways. We confirmed this gene–environment interaction in two birth cohorts, and we ruled out alternative explanations of the finding involving gene–exposure correlation, intrauterine growth, social class, and maternal cognitive ability, as well as maternal genotype effects on breastfeeding and breast milk. The finding shows that environmental exposures can be used to uncover novel candidate genes in complex phenotypes. It also shows that genes may work via the environment to shape the IQ, helping to close the nature versus nurture debate.
The current study's sample:
In all, 5934 children of white European origin had genetic data with additional information on breastfeeding and IQ. Of these 83% were breastfed within the first month. These children had means (SDs) of 108 (16), 100 (17) and 105 (16) for verbal, performance and full-scale IQ respectively.
The breastfeeding association:
Breastfeeding showed a strong association with full-scale IQ with breastfed children scoring 8 points higher IQ on average in unadjusted analyses as has been previously reported [2], [3]. There were strong associations between breastfeeding and most confounders (see Table S2). The breastfeeding effect attenuated to a 3-point advantage after adjustment for these confounders (see Table 2).
The important caveat, referring to this earlier paper by Der et al. From the current paper:
A limitation of this study was the risk of bias due to the lack of controlling for other potentially important factors such as maternal IQ [34], maternal fish consumption during lactation and the ratio of omega-6 to omega-3 fatty acids. These data were not available within ALSPAC. However data on maternal educational qualifications were available. This measure is likely to be highly correlated with maternal IQ and more strongly related than other measures of education such as years of schooling. In addition, adjustment for educational qualifications did not change the conclusions despite being an important predictor of child IQ (p less than 0.001).
What Der et al. had proposed is that smart mothers breastfeed more, so the association between IQ and breastfeeding reflects the heredity of maternal IQ rather than benefits of the breastfeeding practice itself. The current study has used maternal educational qualifications as a proxy for IQ. This is unsatisfactory as education is not as tightly coupled with IQ as would be necessary to let us discount maternal IQ as a source of the breastfed children IQ's increase:

As I have noted in a previous post, extreme care is needed when using proxy variables. You can mentally analyze the IQ-educational attainment relationship into two parts:
  1. Different educational levels (e.g., high school graduates vs. Master's holders) have different average IQ
  2. Within educational levels (e.g., high school graduates) there is variation in IQ. Moreover, there is IQ overlap between educational levels
Using educational level as a proxy for IQ allows us to capture part of the maternal IQ variation. However, if maternal IQ and breastfeeding within an educational level are correlated, then the use of educational level as a proxy for IQ underestimates for the strength of the relationship.

The "meat" of the paper involves the effect of genotype on the IQ/breastfeeding association:

The fact that genotype in the two studied loci modifies the IQ/breastfeeding relationship is evident and needs no further comment.

The discussion of the paper goes into some detail on the technical reasons for the discrepancy between this study and Caspi et al.
PLoS ONE 5(7): e11570. doi:10.1371/journal.pone.0011570

FADS2 Polymorphisms Modify the Effect of Breastfeeding on Child IQ

Colin D. Steer et al.

Breastfeeding is important for child cognitive development. A study by Caspi et al has suggested that rs174575 within the FADS2 gene moderates this effect so that children homozygous in the minor allele (GG genotype) have similar IQs irrespective of feeding method.

Methods and Principal Findings
In our study of 5934 children aged 8 years, no genetic main effect with IQ was found for rs174575. However, an interaction with this polymorphism was observed such that breastfed GG children performed better than their formula fed counterparts by an additional 5.8 points [1.4, 10.1] (interaction p = 0.0091). Interaction results were attenuated by about 10% after adjustment for 7 factors. This study also investigated rs1535, another FADS2 polymorphism in linkage disequilibrium with rs174575, together with performance and verbal IQ, finding similar results although effect sizes were generally reduced.

Conclusions and Significance
This study did not replicate the findings of Caspi et al. In contrast to their study, GG children exhibited the greatest difference between feeding methods such that breastfed children performed similarly irrespective of child genotype whereas formula fed GG children performed worse than other children on formula milk. Further studies are required to replicate these findings.



Unknown said...

5 to 10 points IQ difference? That is VERY significant indeed...

Andrew Oh-Willeke said...

The importance of breast feeding in the GG genotype is suggestive of the notion that GG children are not producing something important to brain development that the other children are producing, which breast milk is replacing. I'd be curious to see if there was a dose-effect response in GG children (i.e. a bigger IQ gap with longer periods of breast feeding).

A model of a deficit solved by breast feeding fits into the larger question of how much of poor IQ in general, and the Flynn effect in particular, is due to environmental factors (e.g. cretinism caused by nutritional deficiencies), something suggested by scholarship showing that hereditary effects on IQ are weaker at very low socioeconomic strata than they are in the more privilege SES strata experienced by participants in twin studies.

Put another way, does most mental retardation have a different in kind cause than ordinary IQ differences between individuals, or is it simply the tail end of the scale? Test scores designed on the assumption of a normal distribution can obscure different in kind or degree differences in IQ between those who a mentally retarded and those who are at a low end of normal variation.

The other thing I wonder is if the measurement of IQ in the children at age 8 is driving the result. Nurture is more important relative to heredity in childhood IQ than it is in adult IQ. Is breast feeding a marker for good nurture generally?