Article

Psychiatric genetics: Progress amid controversy. Nature Reviews Genetics, 9, 527-540

Molecular and Behavioral Neuroscience Institute, University of Michigan, 5061 BSRB, 109 Zina Pitcher Place, Ann Arbor, Michigan 48109-2200, USA.
Nature Reviews Genetics (Impact Factor: 39.79). 08/2008; 9(7):527-40. DOI: 10.1038/nrg2381
Source: PubMed

ABSTRACT Several psychiatric disorders--such as bipolar disorder, schizophrenia and autism--are highly heritable, yet identifying their genetic basis has been challenging, with most discoveries failing to be replicated. However, inroads have been made by the incorporation of intermediate traits (endophenotypes) and of environmental factors into genetic analyses, and through the identification of rare inherited variants and novel structural mutations. Current efforts aim to increase sample sizes by gathering larger samples for case-control studies or through meta-analyses of such studies. More attention on unique families, rare variants, and on incorporating environment and the emerging knowledge of biological function and pathways into genetic analysis is warranted.

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    • "Recently, the NIMH Research Criteria Project suggested that cognition should be one of five core research domains in the field of psychiatric diseases (Morris and Cuthbert, 2012). SCZ and BD are highly heritable disorders (Lichtenstein et al., 2009) with complex genetic and environmental interactions involved (Burmeister et al., 2008). Several lines of research indicate that the immune system may be involved in these interactions (Kinney et al., 2010) and it has been suggested that mononuclear phagocyte cells including microglial cells may play a key role in their pathogenesis. "
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    • "The results of GWAS (Johnson and O'Donnell, 2009) contain many false positives (Burmeister et al., 2008). Current replicable GWAS results account for only a small percentage of the estimated heritability (Ozomaro et al., 2013) and their systematic biological interpretation is lacking. "
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    • "Based on 6 studies of 2509 patients with bipolar I disorder, the weighted mean age of onset falls into 3 groups, having peaks at ages 18.1, 26.9 and 42.7 years, with 55% of patients in the middle or late onset groups (Bellivier et al., 2001, 2003; González Pinto et al., 2009; Hamshere et al., 2009; Lin et al., 2006; Manchia et al., 2008). This broad range of onset and the polygenic basis of bipolar disorder suggest that environmental factors have an influential role (Burmeister et al., 2008; Craddock and Sklar, 2013; Wright et al., 2003). Environmental factors associated with a younger age of onset are cannabis use (González-Pinto et al., 2008; Lagerberg et al., 2011), stressful life events (Horesh et al., 2011) and childhood abuse (Garno et al., 2005; Leverich et al., 2002), while neurological illness is associated with an older onset (Depp and Jeste, 2004). "
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