A Genome-Wide Association Study of First-Episode Psychosis: A Genetic Exploration in an Italian Cohort
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants
2.2. DNA Extraction and Genotyping
2.3. Genomic Analysis
2.4. In Silico Functional Analyses
3. Results
3.1. The PICOS Participants
3.2. Genome-Wide Association Analysis of Non-Affective Psychosis
3.3. In Silico Functional Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Non-Affective Psychosis N = 147, N (%) | Healthy Controls N = 102, N (%) | |
---|---|---|
Sex | ||
Female | 62 (42.2%) | 57 (55.9%) |
Male | 85 (57.8%) | 45 (44.1%) |
Age, years (SD) | - | 33.89 ± 10.99 |
At onset, years (SD) | 29.68 ± 9.04 | - |
Educational level | 10 missing | |
Primary school | 5 (3.6%) | 13 (12.7%) |
Higher school | 132 (96.4%) | 89 (87.3%) |
Living condition | 10 missing | 1 missing |
Alone | 13 (9.5%) | 22 (21.8%) |
With partner and/or children | 27 (19.7%) | 38 (37.6%) |
With parents | - | 33 (32.7%) |
With other relatives | 92 (67.2%) | 1 (1%) |
With other people | 5 (3.6%) | 7 (6.9%) |
Working status | 12 missing | 2 missing |
Employed | 55 (40.7%) | 71 (71%) |
Unemployed | 46 (34.1%) | 10 (10%) |
Student/Retired/Other condition | 30 (25.2%) | 19 (19%) |
Marital status | 16 missing | |
Single | 101 (77.1%) | 54 (52.9%) |
Married | 21 (16.0%) | 40 (39.2%) |
Separated/Divorced | 9 (6.9%) | 8 (7.9%) |
Diagnosis | ||
Schizophrenia | 42 (28.6%) | - |
Other non-affective psychosis | 105 (71.4%) | - |
Chrom | Position (bp) | RSID | Effect Allele | p-Value | Gene | Distance (bp) |
---|---|---|---|---|---|---|
2 | 73,735,674 | rs7606483 | A | 5.9 × 10−14 | ALMS1 | 0 |
2 | 172,897,761 | rs7591150 | G | 7.7 × 10−14 | METAP1D | 0 |
3 | 63,842,629 | rs832190 | A | 8.9 × 10−14 | THOC7 | 0 |
3 | 71,661,862 | rs830650 | A | 8.9 × 10−14 | RP11-154H23.3 | 25,302 |
3 | 80,670,963 | rs72897474 | A | 2.0 × 10−13 | RP11-47P18.1 | 139,230 |
4 | 48,471,170 | rs7670045 | G | 9.4 × 10−14 | ||
5 | 45,882,593 | rs9763350 | A | 2.0 × 10−13 | ||
5 | 46,121,882 | rs8185209 | G | 1.2 × 10−13 | ||
5 | 49,478,029 | rs8188217 | A | 3.5 × 10−13 | ||
5 | 49,674,996 | rs74865196 | A | 2.8 × 10−13 | ||
6 | 23,798,867 | rs9393484 | A | 7.3 × 10−14 | SPTLC1P2 | 58,059 |
6 | 26,211,146 | rs9358912 | A | 1.1 × 10−13 | ||
6 | 26,958,528 | rs9467936 | G | 2.5 × 10−10 | ||
6 | 157,099,430 | A | 2.6 × 10−13 | |||
8 | 8691,622 | rs13270070 | T | 1.5 × 10−13 | MFHAS1 | 0 |
8 | 9620,359 | rs9657509 | A | 9.4 × 10−14 | TNKS | 0 |
8 | 89,588,626 | rs7819570 | A | 8.9 × 10−14 | ||
10 | 104,300,638 | rs9665626 | G | 1.2 × 10−13 | SUFU | 0 |
11 | 133,959,472 | rs12802468 | G | 1.2 × 10−13 | JAM3 | 0 |
14 | 81,735,565 | rs8007595 | A | 2.8 × 10−13 | STON2 | 0 |
16 | 4,515,145 | rs7206782 | A | 8.9 × 10−14 | CDIP1 | 0 |
16 | 74,649,232 | rs8047523 | A | 7.2 × 10−14 | HSPE1P7 | 0 |
18 | 53,301,359 | rs78294462 | A | 2.6 × 10−13 | TCF4 | 0 |
19 | 9,764,421 | rs200076265 | A | 5.9 × 10−12 | ZNF562 | 0 |
19 | 19,358,332 | rs7253952 | A | 4.6 × 10−13 | NCAN | 0 |
19 | 31,045,360 | rs8102611 | A | 1.1 × 10−13 | ZNF536 | 0 |
21 | 33,175,364 | rs62221589 | A | 4.6 × 10−13 |
Trait | RSID | Genes | p-Value | PMID |
---|---|---|---|---|
Schizophrenia | rs7591150 | METAP1D | 7 × 10−7 | 35396580 |
rs72897474 | Intergenic | 8 × 10−8 | 26198764 | |
rs9665626 | SUFU | 5 × 10−9 | 26198764 | |
rs9665626 | ARL3 | 3 × 10−9 | 27922604 | |
rs7206782 | CORO7-PAM16 | 6 × 10−10 | 31740837 | |
rs7206782 | DNAJA3 | 3 × 10−7 | 26198764 | |
rs7206782 | DNAJA3 | 9 × 10−10 | 35396580 | |
rs7253952 | MAU2 | 4 × 10−8 | 30285260 | |
rs9665626 | TRIM8, ARL3 | 4 × 10−10 | 33479212 | |
Waist circumference adjusted for body mass index | rs13270070 | PRAG1, RN7SL178P | 9 × 10−18 | 34021172, 30239722 |
rs9657509 | CLDN23, MFHAS1 | 3 × 10−8 | 34021172 | |
rs7206782 | TNKS | 1 × 10−11 | 34021172 | |
Alcohol dependence | rs3131513 | CLIC4, RUNX3 | 2 × 10−6 | 23942779 |
Autism spectrum disorder | rs9393484 | SPTLC1P2 | 1 × 10−6 | 28540026 |
Bipolar disorder | rs9665626 | SUFU, TRIM8 | 2 × 10−9 | 33479212 |
Depression | rs13270070 | CLDN23, MFHAS1 | 8 × 10−16 | 33859377 |
Educational attainment | rs7606483 | ALMS1P1, RNU6-111P, RPSAP28 | 3 × 10−11 | 35361970 |
General cognitive ability | rs7606483 | RNU6-111P RPSAP28 | 2 × 10−8 | 29844566 |
Neuroticism | rs13270070 | MFHAS1 | 6 × 10−30 | 27067015, 29255261, 29255261 |
Gene Set | N. Genes | β | SE | p-Value | Pbon |
---|---|---|---|---|---|
REACTOME_UREA_CYCLE | 6 | 1.9558 | 0.30306 | 5.6363 × 10−11 | 9.5625 × 10−7 |
ROZANOV_MMP14_TARGETS_DN | 26 | 0.8407 | 0.1762 | 9.2779 × 10−7 | 1.5739 × 10−2 |
ZHAN_MULTIPLE_MYELOMA_MS_DN | 37 | 0.6046 | 0.1401 | 8.0401 × 10−6 | 1.1363 × 10−1 |
GOLDRATH_HOMEOSTATIC_PROLIFERATION | 101 | 0.3758 | 0.0899 | 1.4548 × 10−5 | 2.4678 × 10−1 |
GOBP_REGULATION_OF_DNA_DEMETHYLATION | 10 | 1.0509 | 0.2629 | 3.2099 × 10−5 | 5.4446 × 10−1 |
GOBP_POSITIVE_REGULATION_OF_DNA_DEMETHYLATION | 8 | 1.1283 | 0.2841 | 3.5860 × 10−5 | 6.0822 × 10−1 |
GOBP_POSITIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY | 39 | 0.5700 | 0.1469 | 5.2322 × 10−5 | 8.8738 × 10−1 |
GOBP_POSITIVE_REGULATION_OF_RELEASE_OF_SEQUESTERED_CALCIUM_ION_INTO_CYTOSOL | 32 | 0.5695 | 0.1482 | 6.9526 × 10−5 | 1 |
GOBP_NEGATIVE_REGULATION_OF_NUCLEOCYTOPLASMIC_TRANSPORT | 23 | 0.6782 | 0.1775 | 6.6904 × 10−5 | 1 |
GOBP_POSITIVE_REGULATION_OF_POST_TRANSCRIPTIONAL_GENE_SILENCING | 13 | 1.0190 | 0.2674 | 6.0945 × 10−5 | 1 |
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Treccani, M.; Maggioni, L.; Di Giovanni, C.; Veschetti, L.; Cristofalo, D.; Patuzzo, C.; Lasalvia, A.; Ristic, B.; Kumar, R.; The PICOS-Veneto Group; et al. A Genome-Wide Association Study of First-Episode Psychosis: A Genetic Exploration in an Italian Cohort. Genes 2025, 16, 439. https://doi.org/10.3390/genes16040439
Treccani M, Maggioni L, Di Giovanni C, Veschetti L, Cristofalo D, Patuzzo C, Lasalvia A, Ristic B, Kumar R, The PICOS-Veneto Group, et al. A Genome-Wide Association Study of First-Episode Psychosis: A Genetic Exploration in an Italian Cohort. Genes. 2025; 16(4):439. https://doi.org/10.3390/genes16040439
Chicago/Turabian StyleTreccani, Mirko, Lucia Maggioni, Claudia Di Giovanni, Laura Veschetti, Doriana Cristofalo, Cristina Patuzzo, Antonio Lasalvia, Branko Ristic, Roushan Kumar, The PICOS-Veneto Group, and et al. 2025. "A Genome-Wide Association Study of First-Episode Psychosis: A Genetic Exploration in an Italian Cohort" Genes 16, no. 4: 439. https://doi.org/10.3390/genes16040439
APA StyleTreccani, M., Maggioni, L., Di Giovanni, C., Veschetti, L., Cristofalo, D., Patuzzo, C., Lasalvia, A., Ristic, B., Kumar, R., The PICOS-Veneto Group, Ruggeri, M., Bonetto, C., Malerba, G., & Tosato, S. (2025). A Genome-Wide Association Study of First-Episode Psychosis: A Genetic Exploration in an Italian Cohort. Genes, 16(4), 439. https://doi.org/10.3390/genes16040439