Misleading use of heritability estimates in schizophrenia genetics

A recent paper (Hilker et al., 2018) illustrates how heritability estimates are misused to provide an erroneous impression that schizophrenia is more genetic than it actually is. The same misleading data analyses have been used by prior researchers (Sullivan, Kendler, & Neale, 2003), and have been cited as authoritative up until 2018. Sullivan et al. (2003) reviewed 14 prior twin studies of schizophrenia and concluded that the heritability of schizophrenia is 81%. Hilker et al. (2018) studied 31,524 twin pairs born in Denmark between 1951 and 2000, and found a heritability estimate for schizophrenia of 79%. These findings create an impression that schizophrenia is mostly, if not all genetic. However, when one looks at the actual data in the Methods and Results sections, rather than the conclusions in the Abstract and the Discussion, a very different picture emerges. The actual raw data are: for a diagnosis of schizophrenia, Hilker et al. (2018) found 12 concordant and 69 discordant MZ twin pairs for an MZ concordance rate of 14.8%; they found 12 concordant DZ twin pairs and 355 discordant DZ twin pairs for an overall DZ twin concordance rate of 3.3%. Using the accepted basic formula for calculating heritability (Falconer & MacKay, 1996), this would yield a heritability estimate for schizophrenia of [(14.8% – 3.3% = 11.5%) x 2 = 23%]. The raw concordance data and a heritability estimate of 23% would make it clear that schizophrenia is at most only a little bit genetic. A heritability estimate is a statistical procedure that is based on doubling the difference between MZ and DZ twin concordance rates. This statistic by itself creates an erroneous impression of a larger genetic component to schizophrenia than is indicated by the raw concordance data. What did Hilker et al. (2018) do in order to arrive at a heritability estimate of 79%? First, they manipulated the concordance data. They used a statistical procedure called inverse probability weighting to create concordance rates of 33% for MZ twins and 7% for DZ twins, which they reported in their Abstract and Discussion. These numbers would yield a heritability estimate of [(33% – 7% = 26%) x 2 = 52%]. Since this number would still be unacceptably low, the authors then applied statistical procedures called structural equation modeling and a liability threshold. These procedures involve inserting dummy variables into the equations that inflate the heritability estimate. Such procedures are used throughout the heritability estimate literature going back to Sullivan et al. (2003). One set of authors quotes the preceding studies, which quote the preceding studies, and so on. In many of the papers, the raw concordance data are not even reported because they would conflict with the published heritability estimate. The raw concordance data in Hilker et al. (2018) show that, in their sample, when one identical twin has schizophrenia, the other twin does not have it 85% of the time. This finding, by itself, without any need for further analysis, demonstrates conclusively that schizophrenia can be at most only a little bit genetic. Since this conclusion is unacceptable to authors in the field of