Chasing Ghosts

© : Vera Kuttelvaserova Stuchelova |

© : Vera Kuttelvaserova Stuchelova |

Jay Joseph, a licensed psychologist, has written extensively on the failure of researchers to find scientific evidence that even one psychiatric condition has a genetic basis. In “The Crumbling Pillars of Behavioral Genetics,” he followed the history of failed predictions by Robert Plomin, a genetics researcher, who claimed repeatedly that we were “at the dawn of a new era” in molecular genetics; that “genes associated with behavioral dimensions and disorder are beginning to be identified;” that “within a few years psychology will be awash with genes associated with behavioral disorders.” So far, Plomin and other researchers have got nothing.

Despite the hope that the Human Genome Sequencing Project would “revolutionize the understanding, diagnosis and treatment of most human disorders,” acknowledged polymorphisms (common gene variants) for psychiatric conditions are still nonexistent. In “Still Chasing Ghosts,” Evan Charney said: “Not a single polymorphism has been reliably associated with any psychiatric conditions nor any aspect of human behavior within the ‘normal’ range.” Instead, researchers in psychiatry see schizophrenia and other psychiatric conditions as “multifactorial complex disorders,” meaning that they are caused by a complex interaction of multiple genes and environmental risk factors.

Within an editorial announcing that changes to the journal Neuropsychiatric Genetics, S.S. Farone et al. proudly announced that their journal “has become a leading venue for the publication of high quality research on the genetic basis of neuropsychiatric phenotypes.” But they also acknowledged: “It is no secret that our field has published thousands of candidate gene association studies but few replicated findings.” Joseph commented that in a practical sense, these results are a secret. After the initial results are hyped in the media, the replication failures rarely receive the same media attention. See “The Reproducibility Problem.”

The public has been misled by sensationalized reporting in the popular press, often in concert with leading researchers, to believe that genes for the major psychiatric disorders have been found.

Reluctant to believe the foundational heritability estimates were wrong, genetic researchers have instead hypothesized there is “missing heritability.” Proponents of this position argue that genes (heritability) are present, but cannot be identified (are “missing”) because each gene has such a small effect. So small in fact, that its effect cannot be identified by standard genome-wide association studies (GWAS). Joseph noted that by the summer of 2011 this failure to discover genes underlying psychiatric disorders led 96 of the leading psychiatric researchers to publically plead for potential funding sources to not “give up” on GWAS.

As Joseph pointed out in “Five Decades of Gene Finding Failures in Psychiatry,” the belief in “missing heritability” ignores the possibility that previous conclusions from family, twin and adoption studies could be wrong, all the while assuming that the genes have to exist. Despite evidence that many people diagnosed with “schizophrenia and other psychotic disorders are impacted by trauma, abuse, and other adverse experiences,” there continues to be an almost exclusive focus on “the genetic and biological bases of psychosis.” He suggested that although some researchers claim that several genes for the major psychiatric disorders have now been discovered, “these claims are likely to suffer the same fate as similar non-replicated claims we have heard for decades.” He then quoted John Horgan, a science journalist, who said that since 1990:

Researchers have announced the discovery of ‘genes for’ attention-deficit disorder, obsessive-compulsive disorder, manic depression, schizophrenia, autism, dyslexia, alcoholism, heroin addiction, high IQ, male homosexuality, sadness, extroversion, introversion, novelty seeking, impulsivity, violent aggression, anxiety, anorexia, seasonal affective disorder, and pathological gambling. So far, not one of those claims has been confirmed.

Evan Charney and Jay Joseph (Twin Studies and the “Nonreplication Curse”) described a new methodology, the genome-wide complex trait analysis (GCTA), which has been developed to replace the problems with GWAS. Like a typical GWAS, GCTA scans hundreds of thousands of polymorphisms of thousands of persons. But it does not identify which SNPs [single-nucleotide polymorphisms, common types of genetic variation] are responsible for a trait. Rather, it estimates the total genetic variance by comparing the genetic profiles of a large group of unrelated people. “In other words, it can produce a ‘finding’ of genes even when no specific genes are identified.”

Joseph indicated the GCTA method, like the GWA studies, is based upon two faulty assumptions: 1) the validity of heritability estimates for human behavioral traits and 2) that twin studies and adoption studies have established the genetic basis of psychiatric disorders.

Charney noted that the twin study methodology has been critiqued for making faulty assumptions, like assuming that the environments of MZ (identical) twins were no different than those of DZ (fraternal) twins. In fact, several studies have shown that MZ twins have more similar environments than DZ twins. The equal environment assumption was shown to be false. This environmental difference means that: “trait similarities ascribed to the greater genetic similarity of MZ twins might in fact be due to greater environmental similarity, significantly inflating heritability estimates.” In The Journal of Mind and Behavior, Joseph commented that:

Conclusions in favor of genetics based on twin studies (as well as family studies) were confounded by environmental factors, suggesting that the twin method should have been discarded as an instrument for the detection of genetic influence.

Charney suggested that chasing these “polymorphisms of tiny effect,” in ever-larger studies involving hundreds of thousands of persons, “is the last gasp of a failed paradigm.” It is like chasing ghosts. “Do we really want to squander our time and resources chasing ghosts?”

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