onr:"swepub:oai:prod.swepub.kib.ki.se:149242675"
Sökning: onr:"swepub:oai:prod.swepub.kib.ki.se:149242675" > Genome-wide associa...
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 04670naa a2200817 4500 | |
| 001 | oai:prod.swepub.kib.ki.se:149242675 | |
| 003 | SwePub | |
| 008 | 240701s2022 | |||||||||||000 ||eng| | |
| 024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1492426752 URI |
| 024 | 7 | a https://doi.org/10.1038/s41398-022-01884-32 DOI |
| 040 | a (SwePub)ki | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Okhuijsen-Pfeifer, C4 aut |
| 245 | 1 0 | a Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders |
| 264 | c 2022-04-07 | |
| 264 | 1 | b Springer Science and Business Media LLC,c 2022 |
| 520 | a 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 assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10−3; R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p = 0.01; R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p = 6.84×10−4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p = 8.44×10−3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p = 3.78×10−7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia. | |
| 700 | 1 | a van der Horst, MZ4 aut |
| 700 | 1 | a Bousman, CA4 aut |
| 700 | 1 | a Lin, B4 aut |
| 700 | 1 | a van Eijk, KR4 aut |
| 700 | 1 | a Ripke, S4 aut |
| 700 | 1 | a Ayhan, Y4 aut |
| 700 | 1 | a Babaoglu, MO4 aut |
| 700 | 1 | a Bak, M4 aut |
| 700 | 1 | a Alink, W4 aut |
| 700 | 1 | a van Beek, H4 aut |
| 700 | 1 | a Beld, E4 aut |
| 700 | 1 | a Bouhuis, A4 aut |
| 700 | 1 | a Edlinger, M4 aut |
| 700 | 1 | a Erdogan, IM4 aut |
| 700 | 1 | a Ertugrul, A4 aut |
| 700 | 1 | a Yoca, G4 aut |
| 700 | 1 | a Everall, P4 aut |
| 700 | 1 | a Gorlitz, T4 aut |
| 700 | 1 | a Grootens, KP4 aut |
| 700 | 1 | a Gutwinski, S4 aut |
| 700 | 1 | a Hallikainen, T4 aut |
| 700 | 1 | a Jeger-Land, E4 aut |
| 700 | 1 | a de Koning, M4 aut |
| 700 | 1 | a Lahteenvuo, M4 aut |
| 700 | 1 | a Legge, SE4 aut |
| 700 | 1 | a Leucht, S4 aut |
| 700 | 1 | a Morgenroth, C4 aut |
| 700 | 1 | a Muderrisoglu, A4 aut |
| 700 | 1 | a Narang, A4 aut |
| 700 | 1 | a Pantelis, C4 aut |
| 700 | 1 | a Pardinas, AF4 aut |
| 700 | 1 | a Oviedo-Salcedo, T4 aut |
| 700 | 1 | a Schneider-Thoma, J4 aut |
| 700 | 1 | a Schreiter, S4 aut |
| 700 | 1 | a Repo-Tiihonen, E4 aut |
| 700 | 1 | a Tuppurainen, H4 aut |
| 700 | 1 | a Veereschild, M4 aut |
| 700 | 1 | a Veerman, S4 aut |
| 700 | 1 | a de Vos, M4 aut |
| 700 | 1 | a Wagner, E4 aut |
| 700 | 1 | a Cohen, D4 aut |
| 700 | 1 | a Bogers, JPAM4 aut |
| 700 | 1 | a Walters, JTR4 aut |
| 700 | 1 | a Yagcioglu, EA4 aut |
| 700 | 1 | a Tiihonen, Ju Karolinska Institutet4 aut |
| 700 | 1 | a Hasan, A4 aut |
| 700 | 1 | a Luykx, JJ4 aut |
| 710 | 2 | a Karolinska Institutet4 org |
| 773 | 0 | t Translational psychiatryd : Springer Science and Business Media LLCg 12:1, s. 145-q 12:1<145-x 2158-3188 |
| 856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:149242675 |
| 856 | 4 8 | u https://doi.org/10.1038/s41398-022-01884-3 |
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- Bousman, CA
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- Ayhan, Y
- Babaoglu, MO
- Bak, M
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- van Beek, H
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- Erdogan, IM
- Ertugrul, A
- Yoca, G
- Everall, P
- Gorlitz, T
- Grootens, KP
- Gutwinski, S
- Hallikainen, T
- Jeger-Land, E
- de Koning, M
- Lahteenvuo, M
- Legge, SE
- Leucht, S
- Morgenroth, C
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- Repo-Tiihonen, E
- Tuppurainen, H
- Veereschild, M
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- de Vos, M
- Wagner, E
- Cohen, D
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- Yagcioglu, EA
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