paradox of schizophrenia genetics is a paradigm shift occurring悖论精神分裂症的遗传学是一个范式转变发生.pdfVIP

Doi et al. Behavioral and Brain Functions 2012, 8:28 /content/8/1/28 RESEARCH Open Access Paradox of schizophrenia genetics: is a paradigm shift occurring? 1* 2 3 4 3 3 Nagafumi Doi , Yoko Hoshi , Masanari Itokawa , Takeo Yoshikawa , Tomoe Ichikawa , Makoto Arai , Chie Usui5 and Hirokazu Tachikawa6 Abstract Background: Genetic research of schizophrenia (SCZ) based on the nuclear genome model (NGM) has been one of the most active areas in psychiatry for the past two decades. Although this effort is ongoing, the current situation of the molecular genetics of SCZ seems disappointing or rather perplexing. Furthermore, a prominent discrepancy between persistence of the disease at a relatively high prevalence and a low reproductive fitness of patients creates a paradox. Heterozygote advantage works to sustain the frequency of a putative susceptibility gene in the mitochondrial genome model (MGM) but not in the NGM. Methods: We deduced a criterion that every nuclear susceptibility gene for SCZ should fulfill for the persistence of the disease under general assumptions of the multifactorial threshold model. SCZ-associated variants listed in the top 45 in the SZGene Database (the version of the 23rd December, 2011) were selected, and the distribution of the genes that could meet or do not meet the criterion was surveyed. Results: 19 SCZ-associated variants that do not meet the criterion are located outside the regions where the SCZ-associated variants that could meet the criterion are located. Since a SCZ-associated variant that does not meet the criterion cannot be a susceptibility gene, but instead must be a protective gene, it should be linked to a susceptibility gene in the NGM, which is