Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders
- Okhuijsen-Pfeifer, C
- van der Horst, M Z
- Bousman, C A
- Lin, B
- van Eijk, K R
- Ripke, S
- Ayhan, Y
- Babaoglu, M O
- Bak, M
- Alink, W
- van Beek, H
- Beld, E
- Bouhuis, A
- Edlinger, M
- Erdogan, I M
- Ertuğrul, A
- Yoca, G
- Everall, I P
- Görlitz, T
- Grootens, K P
- Gutwinski, S
- Hallikainen, T
- Jeger-Land, E
- de Koning, M
- Lähteenvuo, M
- Legge, S E
- Leucht, S
- Morgenroth, C
- Müderrisoğlu, A
- Narang, A
- Pantelis, C
- Pardiñas, A F
- Oviedo-Salcedo, T
- Schneider-Thoma, J
- Schreiter, S
- Repo-Tiihonen, E
- Tuppurainen, H
- Veereschild, M
- Veerman, S
- de Vos, M
- Wagner, E
- Cohen, D
- Bogers, J P A M
- Walters, J T R
- Yağcıoğlu, A E Anil
- Tiihonen, J
- Hasan, A
- Luykx, J J
DOIAbstract
Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally...
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