Sunday, June 12, 2011

Genetic testing and potential harm: DTC or trust me I’m a doctor? Recently at a couple of conferences (European Human Genetics conference and Consumer Genetics Conf) there have been various speakers questioning DTC genetics and calling for all health related personal genetics to be delivered through medical practitioners. I argued in the past that unregulated tests delivered through practitioners actually have the potential for more harm, not less. By coincidence last week some discrepancies in a DTC and a via MD test were pointed out to me – and they seem topical.
Breast feeding has many benefits one of which appears to be increased IQ scores – however not all studies agree, some indicating that results may be confounded by maternal intelligence (see Wikipedia). Sometimes inconsistencies in associating an action with an outcome can be resolved by looking at genetic variation (which tends to increase the error bars when not accounted for).
So in 2007 some headlines were made when a study was published by Caspi’s group (PNAS, open access) reporting that there is an increase in IQ but only in infants who were not GG for the FADS2 rs174575 SNP. It seemed like a good study, 2 cohorts whose location could not have been farther apart and nearly 3,000 children tested. The numbers begin to get much smaller though when they are dissected as only approx 8% were homozygous GG:

Interesting results – but just one study and there were some doubts expressed at the time (e.g. “they have a measure of maternal IQ but don't directly include it in the published multiple regression suggests that they tried it, but didn't like the results”)
These are preliminary results but a genetic test is was being offered to medical practitioners to enable “informed decisions” to be made (they don’t cite the study but it must be Caspi). They say:
Genetic testing performed by Existence Genetics enables parents to have access to this extremely useful information about their newborn. Although it may be ideal for most mothers to breastfeed, many are in situations that make the decision not so simple. For example, some women take medications that prevent them from breastfeeding, and others experience pain, poor milk production, and other difficulties.
If the baby doesn’t have this gene then breastfeeding appears to have no effect upon IQ.
Empowered by this groundbreaking research, Existence Genetics now provides women, pediatricians, wet nurses, and lactation consultants with exclusive genetic testing services that will allow them to make a more informed decision about breastfeeding.
Infants who have a specific version of the FADS2 gene will have an increase of approximately 7 IQ points, whereas infants without the variant won’t experience any IQ boost from breastfeeding.
Clearly the only influence that this result could have would be to make it easier for mothers not to breastfeed if there is no IQ benefit. Mothers of FADS2 GG babies will be told that breastfeeding will not increase IQ, there is no difference.
Rule No.1: do not base a genetic test on one study, even if it does look compelling. Break this rule at your peril.
Heres why:
Steer CD, Davey Smith G, Emmett PM, Hibbeln JR, Golding J (2010) FADS2 Polymorphisms Modify the Effect of Breastfeeding on Child IQ. PLoS ONE 5(7): e11570.
In a larger study Steer et al attempted replication in 5,394 children. They were not able to reproduce the results, in fact they reported that breastfed GG children performed better by 5.8 IQ points. GG children actually showed the greatest difference.
And another study:

Martin NW, Benyamin B, Hansell NK, Montgomery GW, Martin NG, Wright MJ, Bates TC. Cognitive function in adolescence: testing for interactions between breast-feeding and FADS2 polymorphisms. J Am Acad Child Adolesc Psychiatry. 2011 Jan;50(1):55-62.e4. Epub 2010 Dec 3.
They also were unable to repeat the Caspi study – unadjusted data showed a benefit if breastfeeding across all genotypes although they also say that when adjusted for sex, SES, paternal and maternal education, and birth weight the significance disappeared – they support the hypothesis that the breastfeeding/IQ association “reflects variation in parental cognitive ability” – in any case there was no FADS2 GG effect.
Based on the follow-up studies there is no support for any personalised advice based on the FADS2 gene – it cannot be used as a reason not to breastfeed and the largest study actually showed increased benefits for IQ in the group that would be advised that not breastfeeding makes no difference
This same doubtful information is also delivered by 23andme: just one study and no mention of the two larger studies. It is though announced as a “preliminary research report”.
I am disappointed that 23andme have not caught the other 2 papers – do they not have an army of researchers keeping up to date? It’s an enormously emotive subject and thus very important, it suggests that they need to improve their literature update methods and I hope they will – try using the “alert me when this article is cited” feature common to almost all journals.
This is does not particularly look good for either of the companies, but there is a big difference – one is delivered by the healthcare practitioner as “useful information” to help you decide to not breastfeed, the other is presented as results of a study. Neither are justified but I would say that the potential for a harmful impact is increased in one of the situations rather than the other. Which has the potential for more harm? Even if you are of the opinion that both are equally harmful, it certainly does not support the claims that because DTC could be harmful it should be banned and all delivered through medical practitioners because that would protect the patient. My view is that DTC or MD is not the problem – transparency is.
I suppose FADS2 is an appropriate name at least
Caspi A, Williams B, Kim-Cohen J, Craig IW, Milne BJ, Poulton R, Schalkwyk LC, Taylor A, Werts H, & Moffitt TE (2007). Moderation of breastfeeding effects on the IQ by genetic variation in fatty acid metabolism. Proceedings of the National Academy of Sciences of the United States of America, 104 (47), 18860-5 PMID: 17984066