TY - JOUR
T1 - DAOA/G72 predicts the progression of prodromal syndromes to first episode psychosis
AU - Mossner, R.
AU - Schuhmacher, A.
AU - Wagner, M.
AU - Quednow, B.B.
AU - Frommann, I.
AU - Kuhn, K.
AU - Schwab, Sibylle
AU - Rietschel, M.
AU - Falkai, P.
AU - Wolwer, W.
AU - Ruhrmann, S.
AU - Bechdolf, A.
AU - Gaebel, W.
AU - Klosterkotter, J.
AU - Maier, W.
PY - 2010
Y1 - 2010
N2 - The genetic factors determining the progressionof prodromal syndromes to first episode schizophrenia haveremained enigmatic to date. In a unique prospective multicentretrial, we assessed whether variants at the D-aminoacid oxidase activator (DAOA)/G72 locus influence progressionto psychosis. Young subjects with a prodromalsyndrome were observed prospectively for up to 2 years toassess the incidence of progression to schizophrenia or firstepisode psychosis. Of the 82 probands with a prodromalsyndrome, 21 probands experienced progression to psychosiswithin the observation period. Assessment of ninecommon variants in the DAOA/G72 locus yielded twovariants with the predictive value for symptom progression:all four probands with the rs1341402 CC genotypedeveloped psychosis compared with 17 out of 78 probandswith the TT or CT genotypes (v2 = 12.348; df = 2;p = 0.002). The relative risk for progression to psychosiswas significantly increased in the CC genotype:RR = 4.588 (95% CI = 2.175–4.588). Similarly, forrs778294, 50% of probands with the AA genotype, but only22% of probands with a GG or GA genotype progressed topsychosis (v2 = 7.027; df = 2; p = 0.030). Moreover,haplotype analysis revealed a susceptibility haplotype forprogression to psychosis. This is one of the first studies toidentify a specific genetic factor for the progression ofprodromal syndromes to schizophrenia, and furtherunderscores the importance of the DAOA/G72 gene forschizophrenia.
AB - The genetic factors determining the progressionof prodromal syndromes to first episode schizophrenia haveremained enigmatic to date. In a unique prospective multicentretrial, we assessed whether variants at the D-aminoacid oxidase activator (DAOA)/G72 locus influence progressionto psychosis. Young subjects with a prodromalsyndrome were observed prospectively for up to 2 years toassess the incidence of progression to schizophrenia or firstepisode psychosis. Of the 82 probands with a prodromalsyndrome, 21 probands experienced progression to psychosiswithin the observation period. Assessment of ninecommon variants in the DAOA/G72 locus yielded twovariants with the predictive value for symptom progression:all four probands with the rs1341402 CC genotypedeveloped psychosis compared with 17 out of 78 probandswith the TT or CT genotypes (v2 = 12.348; df = 2;p = 0.002). The relative risk for progression to psychosiswas significantly increased in the CC genotype:RR = 4.588 (95% CI = 2.175–4.588). Similarly, forrs778294, 50% of probands with the AA genotype, but only22% of probands with a GG or GA genotype progressed topsychosis (v2 = 7.027; df = 2; p = 0.030). Moreover,haplotype analysis revealed a susceptibility haplotype forprogression to psychosis. This is one of the first studies toidentify a specific genetic factor for the progression ofprodromal syndromes to schizophrenia, and furtherunderscores the importance of the DAOA/G72 gene forschizophrenia.
U2 - 10.1007/s00406-009-0044-y
DO - 10.1007/s00406-009-0044-y
M3 - Article
C2 - 19763662
SN - 0940-1334
VL - 260
SP - 209
EP - 215
JO - European Archives of Psychiatry and Clinical Neuroscience
JF - European Archives of Psychiatry and Clinical Neuroscience
IS - 3
ER -