Article

Psychiatric Genetics: A Methodologic Critique

Virginia Institute for Psychiatry and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
American Journal of Psychiatry (Impact Factor: 13.56). 02/2005; 162(1):3-11. DOI: 10.1176/appi.ajp.162.1.3
Source: PubMed

ABSTRACT Psychiatric genetics, which is growing in size and influence within psychiatry, employs four major research paradigms: 1) basic genetic epidemiology, 2) advanced genetic epidemiology, 3) gene finding methods, and 4) molecular genetics. Paradigms 1 and 2 study aggregate genetic risk factors inferred from patterns of resemblance in relatives. Paradigms 3 and 4 study individual susceptibility genes localized on the human genome. Paradigms 1, 2, and 3 are statistical in nature, while paradigm 4 is biological. Genetic risk factors reflect the statistical signals from susceptibility genes. Whether it will be possible to identify all the susceptibility genes that underlie genetic risk factors is uncertain. Furthermore, given current research methods, the inability to detect susceptibility genes cannot disconfirm evidence for genetic risk factors. While paradigms 3 and 4 can provide great explanatory power by tracing etiologic pathways back to basic biological mechanisms, genetic epidemiology can also provide important etiologic insights, albeit of a less basic nature. While paradigms 3 and 4 may eventually replace paradigms 1 and 2, this shift is unlikely to occur quickly. Therefore, the field of psychiatric genetics would do best to integrate these four paradigms, stressing their relative strengths and limitations. This integration can be best done within an overall framework of explanatory pluralism that values a range of reductive explanations across varying levels of biological and psychological complexity.

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    • "Second, our findings of latent G × E also have key implications for molecular genetic research (Kendler, 2005). The suppression of genetic influences by prosocial peer affiliation implies that efforts to identify genetic main effects may be hampered by genetic suppression in particular environmental contexts. "
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    Psychological Medicine 05/2013; 44(4):1-10. DOI:10.1017/S0033291713000974 · 5.43 Impact Factor
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    • "Another often-heard phrase is " the path from genotype to phenotype, " and related metaphors such as the " genetic basis " for X (Hasler et al. 2006; Kendler 2005; MacQueen, Hajek, and Alda 2005). These expressions imply that genes are an organism's starting point, the prime mover, from which causality in ontogeny emanates outwards in space and onwards in time. "
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    • "First, it is important to recognize that the genetic influence on a phenotype (heritability) is not immutable ; it is dependent upon the environment. Indeed, it is most accurate to characterize heritability of an illness in terms of a specific population at a particular point in time (Kendler, 2005). Because different environmental factors may be relevant for different psychiatric illnesses in particular populations, it is difficult to Heritability : ' diseases ' versus behavioral disorders 37 address this limitation effectively. "
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