By Jay Joseph
Schizophrenia researcher Timothy Crow wrote in 2008 that molecular genetic researchers investigating psychotic disorders such as schizophrenia had previously thought that "success was inevitable-one would 'drain the pond dry' and there would be the genes!" But as Crow concluded, "The pond is empty."1 Four years later the psychiatric disorder and psychological trait "gene ponds" appear to have been completely drained, and there are few if any genes to be found. Twenty years ago, however, leading behavioral geneticists had high expectations that molecular genetic research would soon "revolutionize" the behavioral sciences.
During that heady period of the early-1990s, leading behavioral genetic researchers such as Robert Plomin attempted to shift the field's focus towards gene finding efforts. After all, they reasoned, "quantitative genetic" studies of families, twins, and adoptees had established beyond question that variation in "normally distributed" psychological traits such as personality and cognitive ability (IQ), as well as psychiatric disorders and abnormal behavior, had an important genetic component. The decade of the 1990s did in fact witness an explosion of molecular genetic research attempting to pinpoint the genes believed to underlie these traits and disorders. This was followed by the publication of the initial working draft of the human genome sequence in 2001, which many researchers believed would lead to rapid gene discoveries in psychiatry and psychology. According to a pair of prominent researchers, writing in 2003, "Completion of the human genome project has provided an unprecedented opportunity to identify the effect of gene variants on complex phenotypes, such as psychiatric disorders."2 As we approach 2012, however, behavioral genetics and the allied and overlapping field of psychiatric genetics are attempting to come to grips with the stunning failure to discover genes. These fields appear to be approaching a crisis stage, if they are not there already.
Critics, on the other hand, have argued all along that both twin studies and family studies are unable to disentangle the potential roles of genes and environment. They have pointed out for decades that the validity of equal environment assumption (EEA) of the twin method is not supported by the evidence, and that the much more similar environments experienced by reared-together monozygotic (MZ) versus reared-together dizygotic (DZ) twin pairs confound the results of the twin method. Therefore, both family studies and twin studies prove nothing about genetics and their results can be completely explained by non-genetic factors.3 Most behavioral geneticists agree with this assessment as it relates to family studies, but continue to maintain that twin studies provide conclusive evidence that genes play an important role.4 Critics have also pointed to the massive methodological problems and untenable assumptions found in psychological and psychiatric adoption studies, as well as the major problems and environmental confounds in studies of purportedly reared-apart twins.5
Behavioral geneticist Erick Turkheimer described the competing positions of behavioral geneticists and their critics in 2000: Gene discoveries to come would signify behavioral geneticists' "vindication," whereas "critics of behavior genetics expect the opposite, pointing to the repeated failures to replicate associations between genes and behavior as evidence of the shaky theoretical underpinnings of which they have so long complained."6 Turkheimer, however, recognized in 2011, "to the great surprise of almost everyone, the molecular genetic project has foundered on the...shoals of developmental complexity..."7
Behavioral genetics and the related fields have recently adopted the "missing heritability" position to explain the ongoing failure to uncover genes.8 Proponents of this position argue that genes ("heritability") are "missing" because researchers must find better ways to uncover them, as opposed to some critics' contention that the failure to discover genes indicates that these genes do not exist.9 By the summer of 2011 it had reached the point where 96 leading psychiatric genetic researchers, in an open letter, asked potential funding sources not to "give up" on genome-wide association (GWA) studies.10
In light of the ongoing failures of molecular genetic research, it is worthwhile to look back at the way that behavioral geneticists have written about the search for genes, including numerous claims and predictions published in textbooks and leading scientific journals. Here I focus mainly on the writings of the world's leading and most influential behavior geneticist, Robert Plomin of King's College of London, Institute of Psychiatry, who is the lead author of a frequently cited multi-edition textbook on the subject: Behavioral Genetics.11
Three Decades of Claims and Predictions
As far back as 1978, DeFries and Plomin claimed that "Evidence has accumulated to indicate that inheritance of bipolar depression involves X-linkage in some instances."12 Although these and other claims were not replicated, psychiatric molecular genetic research took off in the 1980s, a decade that witnessed many more highly publicized, yet subsequently unsubstantiated, gene finding claims. Nevertheless, another group of prominent behavioral genetic researchers wrote in a 1988 Annual Review of Psychology contribution, ''We are witnessing major breakthroughs in identifying genes coding for some mental disorders.''13
In the 1990 second edition of Behavioral Genetics, Plomin and colleagues wrote, "During the past decade, advances in molecular genetics have led to the dawn of a new era for behavioral genetic research."14 They argued that "these techniques are already beginning to revolutionize behavioral genetic research in some areas, especially psychopathology." However, these "revolutionary advances" were not actual replicated gene findings. Also in 1990, Plomin predicted in Science that "the use of molecular biology techniques will revolutionize behavioral genetics."15
Plomin and his colleagues published a 1994 molecular genetic study in which they found DNA markers associated with IQ.16 However, this study, as well as all subsequent molecular genetic IQ studies, was not replicated.17 In another Science publication, Plomin and colleagues reported genetic linkages and associations for reading disability, sexual orientation, alcoholism, drug use, violence, paranoid schizophrenia, and hyperactivity.18
In the third edition of Behavioral Genetics, published in 1997, the authors repeated their position that psychology is "at the dawn of a new era" on the basis of "molecular genetic techniques."19 For these authors, "nothing can be more important than identifying specific genes involved" in psychological traits and psychiatric disorders. In the same year, Rutter and Plomin wrote that although gene discoveries had not yet been made in psychiatry, "it is obvious that these are likely to be forthcoming very soon as findings with respect to schizophrenia...affective disorder...and dyslexia...all show."20
Plomin and Rutter published a 1998 article in Child Development, where they informed developmental psychologists that "Genes associated with behavioral dimensions and disorders are beginning to be identified."21They added, "as associations between genes and complex behavioral traits are found, they are beginning to revolutionize research." The authors were attempting to prepare psychologists for gene discoveries-in-the-making which they believed would soon revolutionize their field. In another 1998 publication, Plomin and colleagues wrote that a pair of 1996 studies claiming an association between genes and the personality trait of "novelty seeking" constituted a "watershed" event for the field.22
At the dawn of the new millennium, Plomin and Crabbe predicted in 2000 that "within a few years, psychology will be awash with genes associated with behavioral disorders as well as genes associated with variation in the normal range." They also predicted that in the future, clinical psychologists would routinely collect patients' DNA "to aid in diagnosis and to plan treatment programs."23 Elsewhere in 2000, Plomin wrote that genes "are being found for personality...reading disability...and g [general intelligence]...in addition to the main area of research in psychopathology."24 In 2001, at the time of the publication of the first draft of the sequence of the human genome, McGuffin, Riley, and Plomin published an article in Science entitled "Toward Behavioral Genomics,"25 repeating the 1994 claim that gene linkages and associations had been discovered for traits such as aggression, schizophrenia, attention-deficit hyperactivity disorder (ADHD), male homosexuality, and dyslexia. In the same year, Plomin and colleagues published the fourth edition of Behavioral Genetics.26 Here they claimed that "ADHD is one of the first behavioral areas in which specific genes have been identified," and they continued on their theme that "one of the most exciting directions for genetic research in psychology involves harnessing the power of molecular genetics to identify specific genes responsible for the widespread influence of genetics on behavior."
Having entered the "postgenomic era," in 2003 Plomin and McGuffin claimed "progress...towards finding genes....although progress has nonetheless been slower than some had originally anticipated."27 They wrote that the identification of genes for schizophrenia "remains elusive," and the "story for major depression and bipolar depression is similar to schizophrenia." Nevertheless, they continued to believe that the future of molecular genetic research in psychiatry "looks bright because complex traits like psychopathology will be the major beneficiaries of postgenomic developments,"28 although they wrote a year later that researchers would need "very large samples" to uncover genes.29
In the period 2003-2004, Plomin began to write more about gene discoveries as something that had not yet occurred, and less about discoveries that had been made or were in the process of being made. He wrote about "future...molecular genetic studies of DNA that will eventually identify specific DNA variants responsible for the widespread influence of genes in psychological development."30 Elsewhere, he recognized that "no solid" gene associations for IQ "have yet emerged," and that "the road ahead will be much more difficult than generally assumed..."31
Plomin's frustration became more apparent the following year, when he publically asked, in relation to gene finding attempts, "When are we going to be there?" Plomin answered, "Being an optimist, my response is 'soon,'" and recognized that his readers might be "skeptical, because they have heard this before."32 Although Plomin claimed as always that the field was moving toward gene discoveries, he believed that behavioral genetics remained only "on the cusp of a new post-genomic era..." He and his colleagues had decided not to produce a new edition of Behavioral Genetics, he wrote, "until we had some solid DNA results to present."33 Although the next (fifth) edition did report some purported gene associations, the fact that none was replicated meant that they were not so "solid" after all. Currently, some continue to believe, and lament, that we are still on this "cusp."
In a 2010 publication, Haworth and Plomin appeared to give up hope that GWA studies would uncover genes anytime soon, writing that "it seems highly unlikely that most of the genes responsible for the heritability for any complex trait will be identified in the foreseeable future." They added, "we hope that our prediction about GWA research is wrong..." In the process, they fell back on the ad hoc "missing heritability" theory to explain GWA failures.34 Indeed, they recognized that genome-wide association studies "are struggling to identify a few of the many genes responsible for the ubiquitous heritability of common disorders" and psychological traits. In the face of the unexpected and disappointing failures of GWA studies and previous molecular genetic research methods, Haworth and Plomin argued that the field should return its focus to quantitative genetic studies of families, twins, and adoptees, which have a "bright future." Thus, they called for a retreat to previous kinship studies in light of the failures of molecular genetic research, never considering the possibility that the critics were right all along that the massive flaws and untenable theoretical assumptions of these methods explain these failures.
Plomin could not name any replicated gene findings in a 2011 publication, and continued to explain these negative results on the basis of "missing heritability."35 According to Plomin, "The big question now in molecular genetics is how to identify the 'missing' heritability; the big question for non-shared environment is how to identify the 'missing' non-shared environment." As critics have argued, both are "missing" because behavioral geneticists have mistakenly interpreted twin studies as providing unequivocal evidence in favor of genetics. Plomin and his colleagues continue to place total faith in twin research, and continue to ignore the implications of other evidence, which includes Plomin's own carefully performed 1998 longitudinal adoption study that found a non-significant .01 personality test score correlation between birthparents and their 245 adopted-away biological offspring. According to Plomin and his colleagues, this birthparent-biological offspring correlation is "the most powerful adoption design for estimating genetic influence," which "directly indexes genetic influence."36
Conclusion
Science writer John Horgan published a critical appraisal of behavioral genetics in a 1993 edition of Scientific American.37 Horgan noted that although there were many gene finding claims for traits such as crime, bipolar disorder, schizophrenia, alcoholism, intelligence, and homosexuality, none of these claims had been replicated. He presented the results under the heading, "Behavioral Genetics: A Lack-of Progress Report." We can now update Horgan's "progress report" and issue the field of behavioral genetics its apparent final report card: The evidence suggests that genes for the major psychiatric disorders, as well as for IQ and personality, do not exist. As Turkheimer concluded in 2011, in light of the failures of molecular genetic research, it is time to develop a "new paradigm."38
Simply put, the gene finding claims and predictions by Plomin and other leading behavioral geneticists turned out to be wrong. The best explanation for why this occurred is not that "heritability is missing," but that previous and current claims that psychiatric and psychological twin studies prove something about genetics are also wrong.
We cannot expect the proponents of behavioral genetics to recognize that the historical positions of their field are mistaken, that their prized research methods and "landmark" studies are massively flawed and environmentally confounded, and that family, social, cultural, economic, and political environments-and not genetics-are the main causes of psychiatric disorders and variation in human psychological traits. Because most leaders of the field will not allow themselves to see this, it is left to others to show that the pillars of behavioral genetics are crumbling before our very eyes.
We are indeed at the "dawn of a new era," but it will be an era very different than the one that Plomin and his colleagues envisioned.
Jay Joseph, PsyD, is a licensed psychologist and the author of The Gene Illusion and The Missing Gene.
Endnotes
1. Crow, T. J. (2008). The emperors of the schizophrenia polygene have no clothes. Psychological Medicine, 38, 1681-1685.
2. Merikangas, K. R., & Risch, N. (2003). Will the genomics revolution revolutionize psychiatry? American Journal of Psychiatry, 160, 625-635.
3. Joseph, J. (1998). The equal environment assumption of the classical twin method: A critical analysis. Journal of Mind and Behavior,19, 325-358; Joseph, J. (2002). Twin studies in psychiatry and psychology: Science or pseudoscience? Psychiatric Quarterly, 73, 71-82; Joseph, J. (2004). The gene illusion: Genetic research in psychiatry and psychology under the microscope. New York: Algora. (2003 United Kingdom Edition by PCCS Books); Joseph, J. (2006). The missing gene: Psychiatry, heredity, and the fruitless search for genes. New York: Algora; Joseph, J. (2010). Genetic research in psychiatry and psychology: A critical overview. In K. Hood, C. Tucker Halpern, G. Greenberg, & R. Lerner (Eds.), Handbook of developmental science, behavior, and genetics (pp. 557-625). Malden, MA: Wiley-Blackwell;
4. Plomin, R., DeFries, J. C., McClearn, G. E., & McGuffin, P. (2008). Behavioral genetics (5th ed.). New York: Worth Publishers.
5. Joseph, 2004, 2006, 2010. Kamin, L. J. (1974). The science and politics of I.Q. Potomac, MD: Lawrence Erlbaum Associates.
6. Turkheimer, E. (2000). Three laws of behavior genetics and what they mean. Current Directions in Psychological Science, 9, 160-164.
7. Turkheimer, E. (2011). Commentary: Variation and causation in the environment and genome. International Journal of Epidemiology, 40, 598-601.
8. Gershon, E. S., Alliey-Rodriguez, N., & Liu, C. (2011). After GWAS: Searching for genetic risk for schizophrenia and bipolar disorder. American Journal of Psychiatry, 168, 253-256; Haworth, C. M. A., & Plomin, R. (2010). Quantitative genetics in the era of molecular genetics: Learning abilities and disabilities as an example. Journal of the American Academy of Child and Adolescent Psychiatry, 49, 783-793; Manolio, T.A., Collins, F. S., Cox, N. J., Goldstein, D. B., Hindorff, L. A., et al. (2009). Finding the missing heritability of complex diseases. Nature, 461, 747-753; Plomin, R. (2011). Commentary: Why are children in the same family so different? Non-shared environment three decades later. International Journal of Epidemiology, 40, 582-592. For a critical appraisal of “missing heritability,” see Latham, J., & Wilson, A. (2010). The great DNA data deficit: Are genes for disease a mirage? The Bioscience Research Project, retrieved online 12/18/10 from http://www.bioscienceresource.org/commentaries/article.php?id=46
9. Joseph, 2010; Latham & Wilson, 2010.
10. Sullivan, P. F., “On behalf of 96 Psychiatric Genetics investigators.” (2011). Don’t give up on GWAS. Molecular Psychiatry (Advanced online publication, published online 8/9/2011)
11. 5th edition; Plomin, DeFries, McClearn, & McGuffin, 2008.
12. DeFries, J. C., & Plomin, R. (1978). Behavioral genetics. Annual Review of Psychology, 29, 473-515.
13. Loehlin, J. C. , Willerman, L., & Horn, J. M. (1988). Human behavior genetics. Annual Review of Psychology, 39, 101-133.
14. Plomin, R., DeFries, J. C., & McClearn, G. E. (1990). Behavioral genetics: A primer (2nd ed.). New York: W. H. Freeman and Company.
15. Plomin, R. (1990). The role of inheritance in behavior. Science, 248, 183-188.
16. Plomin, R., McClearn, G. E., Smith, D. L., Vignetti, S., Chorney, M. J., Chorney, K., Venditti, C. P., Kasarda, S., Thompson, L. A., Detterman, D. K., Daniels, J., Owen, M., & McGuffin, P. (1994). DNA markers associated with high versus low IQ: The IQ quantitative trait loci (QTL) project. Behavior Genetics, 24, 107-118.
17. Deary, I. J., Penke, L., & Johnson, W. (2010). The neuroscience of human intelligence differences. Nature Reviews Neuroscience, 11, 201-211.
18. Plomin, R., Owen, M. J., & McGuffin, P. (1994). The genetic basis of complex behaviors. Science, 264, 1733-1739.
19. Plomin, R., DeFries, J. C., McClearn, G. E., & Rutter, M. (1997). Behavioral genetics (3rd ed.). New York: W. H. Freeman and Company.
20. Rutter, M., & Plomin, R. (1997). Opportunities for psychiatry from genetic findings. British Journal of Psychiatry, 171, 209-219.
21. Plomin, R., & Rutter, M. (1998). Child development, molecular genetics, and what to do with genes once they are found. Child Development, 69, 1223-1242.
22. Plomin, R., Corley, R., Caspi, A., Fulker, D. W., & DeFries, J. C. (1998). Adoption results for self-reported personality: Evidence for nonadditive genetic effects? Journal of Personality and Social Psychology, 75, 211-218.
23. Plomin, R., & Crabbe, J. (2000). DNA. Psychological Bulletin, 126, 806-828.
24. Plomin, R. (2000). Behavioural genetics in the 21st century. International Journal of Behavioral Development, 24, 30-34.
25. McGuffin, P., Riley, B., & Plomin, R. (2001). Towards behavioral genomics. Science, 291, 1232-1249.
26. Plomin, R., DeFries, J. C., McClearn, G. E., & McGuffin, P. (2001). Behavioral genetics (4th ed.). New York: Worth Publishers.
27. Plomin, R., & McGuffin, P. (2003). Psychopathology in the postgenomic era. Annual Review of Psychology, 54, 205-228.
28. Plomin, R. (2003). General cognitive ability. In R. Plomin, J. DeFries, I. Craig, & P. McGuffin (Eds.), Behavioral genetics in the postgenomic era (pp. 183-201). Washington, DC: American Psychological Association Press.
29. McGuffin, P., & Plomin, R. (2004). A decade of the Social, Genetic and Developmental Psychiatry Centre at the Institute of Psychiatry. British Journal of Psychiatry, 185, 280-282.
30. Plomin, R. (2004). Genetics and developmental psychology. Merrill-Palmer Quarterly, 50, 341-352.
31. Plomin, R., & Spinath, F. M. (2004). Intelligence: Genetics, genes, and genomics. Journal of Personality and Social Psychology, 86, 112-129.
32. Plomin, R. (2005). Finding genes in child psychology and psychiatry: When are we going to be there? Journal of Child Psychology and Psychiatry, 46, 1030-1038. (In this quote, Plomin was referring to his “What To Do with Genes Once They are Found” 1998 publication co-authored with Rutter.)
33. Plomin, 2005.
34. Haworth & Plomin, 2010.
35. Plomin, 2011.
36. Plomin, Corley, Caspi, Fulker, & DeFries, 1998.
37. Horgan, J. (1993). Eugenics revisited. Scientific American, 268 (6), 122-131.
38. Turkheimer, 2011.
Thank You Council for Responsible Genetics and Mr Joseph
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