Jump the gun and you will be shot down

28 November 2015

“What”, asks clinical psychologist Oliver James, “would lead to acceptance of the null hypothesis of the Human Genome Project as regards psychological traits?”. The answer to this question is “a scientific literature that looks very different indeed to the existing one”. In his letter, James exploits the complex nature of behaviour genetics to sow confusion about what geneticists have found. In an attempt to clear up some of that confusion, below is a point-by-point rebuttal to each one of his arguments.

James: “The hypothesis of the Human Genome Project (HGP) was that differences in DNA sequences would significantly explain why one individual is more likely to possess a trait than another. This has been proven to be true for some physical differences, such as anatomical ones, like height. But, so far, there are no psychological traits – none at all – which have been shown to be significantly influenced by specific variations in DNA (James, 2016).”

It is very odd to concede that genes influence height, but then deny that the same is true for psychological traits, because the evidence for both inferences comes from exactly the same scientific methodology. All kinds of behaviour-genetic investigations (twin studies, family pedigree studies, adoption studies, and newer DNA-based studies) show consistent results when it comes to height and to psychological traits such as IQ, personality, and many other psychological measures. Physical and psychological traits are both under substantial genetic influence. I will get to James’s statement about “specific variations in DNA” below.

James: “Robert Plomin, the most widely cited authority in this field in the UK, told the Guardian newspaper in 2014 that, as regards psychological traits, ‘I have been looking for these genes for fifteen years and I don’t have any’ (Wilby, 2014).”

This is an out-of-context quote mine. To be clear, because this is a source of some confusion: we can know that a trait is genetically influenced (from methods such as twin studies) without knowing the specific genes involved (knowledge about which comes from different methods, such as genome-wide association studies). Thus, Robert Plomin is noting that, whereas we know that many psychological traits are strongly heritable, we do not yet know the specific genes involved (the reason for this is that very large studies are needed to have the statistical power to detect specific genetic associations; these take longer to put together than the average study). There is nothing contradictory or surprising about this.

In any case, James is out of date: genome-wide association studies in 2014 and 2015 have uncovered specific genes related to educational performance, to IQ and to the personality trait of neuroticism. Even larger studies with even more impressive genetic results are on the way.

James: “Genome Wide Association (GWA) studies have scanned up to a million sites on the individual genomes of tens of thousands of subjects. Whilst some variant DNA sequences have been established as associated with specific traits and in some cases that has been replicated, they provide negligible heritability: when the effect of the variants is summed all together, they produce heritability estimates of only 1–5 per cent (James, 2014, 2016). It seems highly probable that GWA studies will find no significant role for genes.”

Again, James elides ‘knowing a trait is heritable’ with ‘knowing the specific genes involved’. Since we are only at the very beginning of our use of genome-wide association studies, and since very large samples are needed to detect the very many genetic variants that relate to psychological traits, nobody sensible should expect that we would know a large proportion of them by now. Just take a look at Figure 1 in this short Nature article. As sample sizes have increased, so have the number of genetic variants found (in this case linked to schizophrenia).page1image32800page1image32960page1image33120page1image33280page1image33440page1image33600page1image33760page1image33920
James asserts that it is ‘highly probable’ that this progress in genetics will come to a halt. I suggest that this quotation could be added to this webpage of ‘incorrect predictions’, alongside the statement from the New York Times in 1920 that ‘a rocket will never be able to leave the Earth’s atmosphere’.

James: The only other approach which still holds out hope that DNA directly effects individual differences in psychological traits are gene–environment interaction studies of candidate genes. Studies of epigenetics, junk genes or Genome Wide Complex Trait Analysis (GCTA) do not test the HGP hypothesis because they do not link specific DNA sequences to any specific trait outcomes (James, 2014).

I have no idea what epigenetics or junk genes have to do with James’s argument, here: he appears to have thrown them in in an attempt to sound more scientific. He does, however, mention the method of Genome-Wide Complex Trait Analysis (GCTA). GCTA is a purely DNA-based method that tests whether individuals who are similar in DNA variants are also similar in their phenotypic traits. It allows estimation of the heritability of psychological traits without the assumptions of twin and family methods – assumptions that James has been attacking for years. That is, GCTA is a compelling piece of evidence against James’s worldview, but he does not appear to have realized it. For the third time, we do not need to know which specific DNA sequences relate to a trait to know it is heritable.

James: Although there have been some promising results in gene-environment studies (Belsky et al., 2009; Rutter, 2014), there have been a great many non-replications. Of 103 gene– environment studies of candidate genes conducted between 2000 and 2009, only 27 per cent of attempts to replicate proved positive (Duncan & Keller, 2013). When the direct impact of candidate genes for a variety of traits was reviewed in 100 GWA studies, very little effect was identified (Siontis et al., 2010).

Another complexity in the scientific literature; another opportunity for James to mislead. The era of ‘candidate gene’ studies, where scientists tested relations between specific, theoretically-relevant genes and phenotypic traits, did indeed have a replicability problem, as the cited Duncan and Keller (2013) study—which, incidentally, is an excellent example of behavioural geneticists carefully considering the replicability of their field—discusses. The cited Siontis et al. (2010) study backs this up, though notes that some pre-2010 candidate gene studies were worth following up. Importantly, however, researchers have learned the lessons and moved on from candidate gene studies, towards genome-wide association studies. And as noted above, these have had recent success in finding genes linked to psychological traits.

James: It is quite possible that the gene–environment hypothesis will never be supported, or only be shown to have a minor influence on psychological outcomes. At first, when the HGP had consistently found trivial or nonexistent heritabilities, the large gulf between those findings and those of twin studies was labelled Missing Heritability (Manolio et al., 2009). The evidence is increasingly suggesting the heritability is not missing; it is non-existent.

The idea of the ‘missing heritability’ refers to the fact that we know, from twin and family studies, that many traits are highly heritable, but we do not yet know the specific genes involved. That is, if one adds up the contributions of all the genes we know about that are related to a trait, they do not explain as much variation as we’d expect from the twin study estimate. But as I argued above, we should not expect to have found the vast bulk of these genes by now. This is principally because of the huge sample sizes required to find genes for complex traits: James is once again jumping the gun quite spectacularly to suggest that progress in genetics is about to dry up. page2image31960page2image32120page2image32280page2image32440

James: There have always been grave doubts about the robustness of the twin method (Joseph, 2015; James, 2016). It is possible that twin studies will turn out to have been conflating supposedly high heritability with shared environmental factors. THISE analysis – Twin Studies’ ‘Heritability’ Is Shared Environment – proposes that twin study heritability findings really indicate that for this trait, parents treat their children more similarly (James, 2014). A great deal of what has been assumed to be genetic influence could be the consequence of identical twins being treated more similarly than non-identical twins: the obvious implication of the HGP findings is that the equal environments assumption is false, a proposition which already had considerable evidence to support it before the HGP (Joseph, 2015).

And yet, the evidence for the heritability of psychological traits comes not just from twin studies, but from adoption studies, family-pedigree studies, and, as noted above, directly from DNA (the GCTA method). The estimates from all these different designs, all of which entail different assumptions, hang together remarkably well. All these issues were discussed in a recent debate in the criminology literature: see this paper for a resounding defence of twin methodology. Incidentally, a review of the cited book by Joseph (2015) by behavioural geneticist Eric Turkheimer is available here and is well worth reading.

James: At the end of the newspaper interview with Robert Plomin he was asked what he would conclude if the genes he is looking for are never found. Plomin replied: ‘I will still believe that [genetic] heritability is true’. This sounds more like faith than science. Whilst it is impossible to prove a negative, what will be regarded as sufficient evidence that the null hypothesis of the HGP should be accepted? It behoves the likes of Plomin to tell us.

In a crowning irony, James - who has spent decades flailing, Canute-like, against a tide of genetic evidence disconfirming his cherished beliefs - accuses another person of an attitude “more like faith than science”. For the fourth time, James is confusing evidence of heritability with evidence for specific genes. Bearing that in mind, Plomin’s statement is not outrageous in the slightest. Of course, as I noted above, we are beginning to find specific genes related to psychological traits, so the journalist’s question to Plomin is moot.

James: In the meantime, the practice of beginning scientific articles with the assertion that such traits as intelligence, ADHD and schizophrenia are ‘highly heritable’, based purely on studies of twins or adoptees, should be ended. This assertion is simply no longer tenable in the light of the HGP findings.

To recap: evidence from a huge range of different methodologies, using families and twins, speaks to the high heritability of traits like IQ, ADHD, and schizophrenia. The fact that we do not yet know many of the specific genetic variants that explain these traits and disorders —though the numbers are increasing all the time—says nothing about this heritability. James’s argument boils down to “show me the genes!”. It seems safe to say that he will look even sillier in a few years, when many of these genes are known.

James: Similarly, undergraduate and secondary education courses should cease teaching that any psychological traits are ‘highly’ heritable. At the very least, it should be explained that the HGP findings pose a major challenge to that claim.

In this final paragraph, James proposes that we should teach students to be as confused as he is about behaviour genetics. On the basis of all the evidence cited above, I can’t say that I agree.

Stuart J. Ritchie
The University of Edinburgh