Abstract
This chapter describes the history of modern-day psychiatric genetics, beginning with the linkage studies of the late 1980s, the candidate-gene studies of the 1990s, and the genome-wide association studies that continue to the present day. Despite all the media hype, scientists have not found one gene for mental illness, because no such gene exists. The meaning of the phrase “a gene for” mental illness or any other trait is discussed. This chapter features my visit to the laboratory of Richard Huganir, Director of both the Department of Neuroscience and the Kavli Neuroscience Discovery Institute at the Johns Hopkins Medical Institutions.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Notes
- 1.
“International Consortium Completes Human Genome Project,” National Human Genome Research Institute, accessed July 25, 2018. https://www.genome.gov/11006929/2003-release-international-consortium-completes-hgp/
- 2.
“Grassley probes financing of advocacy group for mental health,” Mind Freedom, accessed September 1, 2018, http://www.mindfreedom.org/kb/psych-drug-corp/nami/grassley-nami
- 3.
Francis S. Collins “The Genome Era and Mental Illness,” NAMI Advocate, (Summer/Fall 2003): 29–30, https://www.genome.gov/pages/news/documents/genomemental.pdf, 29.
- 4.
Albert De La Chapelle et al., “A Deletion in Chromosome 22 Can Cause DiGeorge Syndrome,” Human Genetics, 57, no. 3 (1981): 253–256.
- 5.
Deborah A. Driscoll et al., “Deletions and Microdeletions of 22q11.2 in Velo-Cardio-Facial Syndrome,” American Journal of Medical Genetics, 44, no. 2 (September 15, 1992): 262–268, https://doi.org.10.1002/ajmg.1320440237; J. Burn et al., “Conotruncal Anomaly Face Syndrome Is Associated With a Deletion Within Chromosome 22q11,” Journal of Medical Genetics 30, no. 10 (October 1993): 822–824.
- 6.
Donna M. McDonald-McGinn and Kathleen Sullivan, “Chromosome 22q11.2 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome),” Medicine, 90, no. 1 (January 2011): 1–18
- 7.
Ibid., 9.
- 8.
Anat Horowitz et al., “A Survey of the 22q11 Microdeletion in a Large Cohort of Schizophrenia Patients,” Schizophrenia Research, 73, no. 2–3 (March 1, 2005): 263–267, https://doi.org/10.1016/j.schres.2004.02.008, 263.
- 9.
De La Chapelle et al., “A Deletion in Chromosome 22,” 253–256.
- 10.
Janice A. Egeland et al., “Bipolar Affective Disorders Linked to DNA Markers on Chromosome 11,” Nature, 325, no. 6107 (February 26 – March 4, 1987): 783–787, https://doi.org/10.1038/325783a0
- 11.
Robin Sherrington et al., “Localization of a Susceptibility Locus for Schizophrenia on Chromosome 5,” Nature, 336, no. 6195 (November 10, 1988): 164–167, https://doi.org/10.1038/336164a0
- 12.
Anonymous, “Where Next With Psychiatric Illness?” Nature, 336, no. 6195 (November 10, 1988), 95, https://doi.org/10.1038/336095a0
- 13.
Ibid., 96.
- 14.
John R. Kelsoe et al., “Re-Evaluation of the Linkage Relationship Between Chromosome 11p Loci and the Gene for Bipolar Affective Disorder in the Old Order Amish,” Nature, 342, no. 6247 (November 16, 1989): 238–243, https://doi.org/10.1038/342238a0; Michele C. LaBuda et al., “A Follow-Up Report of a Genome Search for Affective Disorder Predisposition Loci in Old Order Amish,” American Journal of Human Genetics, 59, no. 6 (1996): 1343–1362, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1914888/
- 15.
James L. Kennedy et al., “Evidence Against Linkage of Schizophrenia to Markers on Chromosome 5 in a Northern Swedish Pedigree,” Nature, 336, no. 6195 (November 10, 1988): 167–170, https://doi.org/10.1038/336167a0; Peter McGuffin et al. “Exclusion of a Schizophrenia Susceptibility Gene From the Chromosome 5q11-q13 Region: New Data and a Reanalysis of Previous Reports,” American Journal of Human Genetics, 47, no. 3 (September 1990): 524–535; Michael J. Owen, David Crauford, and David St. Clair, “Localisation of a Susceptibility Locus for Schizophrenia on Chromosome 5,” British Journal of Psychiatry, 157, no. 1 (July 1990): 123–127, https://doi.org/10.1192/bjp.157.1.123; G. Kalsi et al. “New DNA Markers With Increased Informativeness Show Diminished Support for a Chromosome 5q11-13 Schizophrenia Susceptibility Locus and Exclude Linkage in Two New Cohorts of British and Icelandic Families,” Annals of Human Genetics, 63, (May 1999): 235–247.
- 16.
Harold M. Schmeck, Jr., “Defective gene tied to form of manic-depressive illness.” New York Times, February 26, 1987, https://www.nytimes.com/1987/02/26/us/defective-gene-tied-to-form-of-manic-depressive-illness.html
- 17.
Natalie Angier, “Scientists Now Say They Can’t Find a Gene For Manic Depressive Illness.” New York Times, January 13, 1993, https://www.nytimes.com/1993/01/13/health/scientists-now-say-they-can-t-find-a-gene-for-manic-depressive-illness.html
- 18.
Harold M. Schmeck, Jr., “Schizophrenia Study Finds Strong Signs of Hereditary Cause.” New York Times, November 10, 1988, https://www.nytimes.com/1988/11/10/us/schizophrenia-study-finds-strong-signs-of-hereditary-cause.html
- 19.
Harold M. Schmeck, Jr., “Scientists Now Doubt They Found Faulty Gene Linked to Mental Illness.” New York Times, November 7, 1989, https://www.nytimes.com/1989/11/07/science/scientists-now-doubt-they-found-faulty-gene-linked-to-mental-illness.html
- 20.
Shorter, History, 246.
- 21.
Michael J. Owen, “Will Schizophrenia Become a Graveyard for Molecular Geneticists?” Psychological Medicine, 22, no. 2 (May 1992): 289–293.
- 22.
Steven A. McCarroll, Goping Feng, and Steven Hyman, “Genome-Scale Neurogenetics: Methodology and Meaning,” Nature Neuroscience, 17, no. 6 (June 2014): 759, https://doi.org/10.1038/nm.3716
- 23.
John P.A. Ioannidis, “Why Most Published Research Findings Are False,” PLoS Medicine, 2, no. 8 (August 2005): 696–701, https://doi.org/10.1371/journal.pmed.0020124
- 24.
Steven A. McCarroll, Goping Feng, and Steven Hyman, “Genome-Scale Neurogenetics,” 759, https://doi.org/10.1038/nm.3716
- 25.
Patrick F. Sullivan, “The Psychiatric GWAS Consortium: Big Science Comes to Psychiatry,” Neuron, 68, no. 2 (October 21, 2010): 183, https://doi.org/10.1016/j.neuron.2010.10.003
- 26.
Robert Plomin and John Crabbe, “DNA,” Psychological Bulletin, 126, no. 6 (November 2000): 806.
- 27.
Patrick F. Sullivan, “Psychiatric GWAS Consortium,” 183.
- 28.
Katherine E. Tansey, Michael J. Owen, and Michael C. O’Donovan, “Schizophrenia Genetics: Building the Foundations of the Future,” Schizophrenia Bulletin, 41, no. 1 (2015): 15, https://doi.org/10.1093/schbul/sbu162
- 29.
Schizophrenia Working Group of the Psychiatric Genetics Consortium, “Biological Insights From 108 Schizophrenia-Associated Genetic Loci,” Nature, 511, no. 7510 (July 24, 2014): 421–427, https://doi.org/10.1038/nature13595
- 30.
International Schizophrenia Consortium, “Common Polygenic Variation Contributes to the Risk of Schizophrenia That Overlaps With Bipolar Disorder,” Nature, 460, no. 7256 (August 6, 2009): 748–752, https://doi.org/10.1038/nature08185; Huang et al., “Cross-Disorder Genomewide Analysis of Schizophrenia, Bipolar Disorder, and Depression,” American Journal of Psychiatry, 167, no. 10 (October 2010): 1254–1263, https://doi.org/10.1176/appi.ajp.2010.09091335; Cross-Disorder Group of the Psychiatric Genetics Consortium, “Identification of Risk Loci With Shared Effects on Five Major Psychiatric Disorders: a Genome-Wide Analysis,” Lancet, 381, no. 9875 (April 20, 2013): 1371–1379, https://doi.org/10.1016/S0140-6736(12)62129-1; Lee et al., “Genetic Relationship Between Five Psychiatric Disorders Estimated From Genome-Wide SNPs,” Nature Genetics, 45, no. 9 (August 11, 2013): 984–994, https://doi.org/10.1038/ng.2711; Steven A. McCarroll, Goping Feng, and Steven Hyman, “Genome-Scale Neurogenetics,” 757; Henriksen et al., “Genetics of Schizophrenia: Overview of Methods, Findings and Limitations,” Frontiers in Human Neuroscience, 11, (2017): 326, https://doi.org/10.3389/fnhum.2017.00322; Brainstorm Consortium, “Analysis of Shared Heritability in Common Disorders of the Brain,” Science, 360, no. 6395 (June 22, 2018): https://doi.org/10.1126/science.aap8757
- 31.
Kenneth Kendler, “‘A Gene For…:’ The Nature of Gene Action in Psychiatric Disorders,” American Journal of Psychiatry, 162, no. 7 (July 2005): 1243–1252, https://doi.org/10.1176/appi.ajp.162.7.1243
- 32.
Daniel Weinberger informed me the “significant genes”—the ones that reached the p = 10−8 level of significance—account for 2 or 3 percent of the liability to schizophrenia in the general population. Dr. Weinberger is Director and CEO of the Lieber Institute for Brain Development and the Maltz Laboratories as well as Professor of Psychiatry, Neurology, Neuroscience, and Human Genetics at JHMI. See Chap. 14 of this volume for my conversation with him.
- 33.
Jay Joseph, “The ‘Missing Heritability’ of Psychiatric Disorders: Elusive Genes or Non-Existent Genes?” Applied Developmental Science, 16, no. 2 (April 2012): 65–83, https://doi.org/10.1080/10888691.2012.667343
- 34.
Ibid., 75–76.
- 35.
L.L. Heston, “Psychiatric Disorders in Foster Home Reared Children of Schizophrenic Mothers,” British Journal of Psychiatry, 112, no. 489 (August 1966): 819–825.
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2019 The Author(s)
About this chapter
Cite this chapter
Hahn, P.D. (2019). The Human Genome Project Era. In: Madness and Genetic Determinism. Palgrave Macmillan, Cham. https://doi.org/10.1007/978-3-030-21866-9_7
Download citation
DOI: https://doi.org/10.1007/978-3-030-21866-9_7
Published:
Publisher Name: Palgrave Macmillan, Cham
Print ISBN: 978-3-030-21865-2
Online ISBN: 978-3-030-21866-9
eBook Packages: Behavioral Science and PsychologyBehavioral Science and Psychology (R0)