Genome‐wide association analysis of age at onset in schizophrenia in a European‐American sample

Wang, Ke Sheng; Li, Xuefeng; Zhang, Qunyuan; Aragam, Nagesh; Pan, Yue

doi:10.1002/ajmg.b.31209

Cited by 29 publications

(25 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AGXT2L1 was down-regulated in suicide completers (46) and in 72% of major depressive disorder: suicide cases compared with agematched controls (47). A genome-wide association analysis indicated the association of schizophrenia with SNPs in the region of the COL25A1 gene, near the AGXT2L1 gene, on chromosome 4q25 (48). AGXT2L1 was the most up-regulated gene in a genome-wide expression study following 2 weeks of lithium administration to mice (49).…”

Section: Discussionmentioning

confidence: 95%

Molecular Identification of Hydroxylysine Kinase and of Ammoniophospholyases Acting on 5-Phosphohydroxy-l-lysine and Phosphoethanolamine

Veiga‐da‐Cunha

Hadi

Balligand

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Vertebrate genomes encode AGXT2L1 and AGXT2L2, two related, pyridoxal-phosphate dependent enzymes of unknown function. Results: Comparison with bacterial genomes suggested that AGXT2L1 and AGXT2L2 are ammoniophospholyases functionally related with AGPHD1. The three recombinant proteins were produced and studied. Conclusion: AGXT2L1 is O-phosphoethanolamine phospholyase; AGXT2L2 is 5-phosphohydroxy-L-lysine phospholyase; AGPHD1 is 5-hydroxylysine kinase. Significance: These molecular identifications will help explain some specific neurometabolic diseases.

show abstract

Section: Discussionmentioning

confidence: 95%

Molecular Identification of Hydroxylysine Kinase and of Ammoniophospholyases Acting on 5-Phosphohydroxy-l-lysine and Phosphoethanolamine

Veiga‐da‐Cunha

Hadi

Balligand

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Attempts to replicate the top loci for our AAO analyses in the Psychiatric Genomics Consortium yielded no additional support. The prior GWAS of AAO in a European–American sample reported association signals at 8q24.22, 4q25 in COL25A1 , and 4p16.1 near RAF1P1 (Wang et al, 2011). Results for two of the reported SNPs in these regions were available in the present study, but failed to support association at these loci (rs7819815 at 8q24.22, p = .103; rs17407555 at 4p16.1, p = .616).…”

Section: Discussionmentioning

confidence: 96%

“…Aside from one study of AAO (Wang et al, 2011), these measures have been untested in a GWAS framework. Although results did not surpass genome-wide thresholds of significance, several strong association signals were observed.…”

Section: Discussionmentioning

confidence: 99%

Genetic modifiers and subtypes in schizophrenia: Investigations of age at onset, severity, sex and family history

Bergen

Ó'Dúshláine

Lee

et al. 2014

Schizophrenia Research

View full text Add to dashboard Cite

Schizophrenia is a genetically and clinically heterogeneous disorder. Genetic risk factors for the disorder may differ between the sexes or between multiply affected families compared to cases with no family history. Additionally, limited data support a genetic basis for variation in onset and severity, but specific loci have not been identified. We performed genome-wide association studies (GWAS) examining genetic influences on age at onset (AAO) and illness severity as well as specific risk by sex or family history status using up to 2762 cases and 3187 controls from the International Schizophrenia Consortium (ISC). Subjects with a family history of schizophrenia demonstrated a slightly lower average AAO that was not significant following multiple testing correction (p = .048), but no differences in illness severity were observed by family history status (p = .51). Consistent with prior reports, we observed earlier AAO (p = .005) and a more severe course of illness for men (p = .002). Family history positive analyses showed the greatest association with KIF5C (p = 1.96 × 10−8), however, genetic risk burden overall does not differ by family history. Separate association analyses for males and females revealed no significant sex-specific associations. The top GWAS hit for AAO was near the olfactory receptor gene OR2K2 (p = 1.52 × 10−7). Analyses of illness severity (episodic vs. continuous) implicated variation in ST18 (p = 8.24 × 10−7). These results confirm recognized demographic relationships but do not support a simplified genetic architecture for schizophrenia subtypes based on these variables.

show abstract

“…Through 2 separate genome-wide association analyses, COL25A1 has been proposed as a candidate to influence the age of onset of schizophrenia and has been associated with the development of antisocial personality disorder in adults with substance abuse [Wang et al, 2011;Li et al, 2012]. The variability in mental health pathologies reported is consistent with the complex behavioral phenotype encountered in the 3 presently discussed patients.…”

Section: Discussionmentioning

confidence: 80%

“…The studies of Groenestege et al [2007] , Wang et al [2011], and Futamura et al [2002] reveal there is support that combined loss of EGF and COL25A1 may act as a '2-hit' scenario, increasing the likelihood of schizophrenia. This combined effect may explain the 20-year-old patient's 'obsessive ritualistic behaviors… [and] vague ideas of reference and 'auditory hallucinations',' traits absent in our reported family [Verhoeven et al, 2013].…”

Section: Discussionmentioning

confidence: 99%

A Rare Recurrent 4q25 Proximal Deletion Not Involving the PITX2 Gene: A Genomic Disorder Distinct from Axenfeld-Rieger Syndrome

2016

View full text Add to dashboard Cite

A de novo 1.2 Mb-4q25 proximal microdeletion encompassing the genes COL25A1 and ELOVL6 has been reported once in a 20-year-old woman. She had dysmorphic features and a complex behavioral phenotype, as described in table 1 [Verhoeven et al., 2013]. Through genotype-phenotype correlation, COL25A1 and EGF were proposed as candidate genes responsible for her unique phenotype [Verhoeven et al., 2013]. Prior to that publication, 4q25 microdeletion syndrome was mostly associated with Axenfeld-Rieger syndrome, with 95% of the affected patients having mutations or deletions involving the PITX2 gene or related upstream regulatory genes, often in a haploinsufficient manner [Amendt et al., 2000;Becker et al., 2003]. Here, we report on 2 additional patients (a child and his mother) having a smaller, but overlapping deletion characterized by a common behavioral and physical phenotype. The 3 patients combined suggest the existence of a novel 4q25 proximal deletion syndrome. Patients and Methods Clinical Case FindingsA 29-month-old Caucasian boy presented to our clinic with his 19-year-old mother. His medical history included birth via Cesarean section for fetal distress, eczema, and seasonal allergies. Key Words COL25A1 · Developmental delay · EGF · Hypotelorism · Hypotonia · Mandible asymmetry · Microdeletion 4q25Abstract Haploinsufficient microdeletions within chromosome 4q25 are often associated with Axenfeld-Rieger syndrome. A de novo 4q25 deletion, 675 kb proximal to PITX2 , has previously been reported once in an adult patient. The patient did not have Axenfeld-Rieger anomaly, but instead had intellectual disability and a complex behavioral phenotype with withdrawn, stereotypic, and ritualistic behavior. Array comparative genome hybridization demonstrated a smaller, overlapping 4q25 deletion in a 2-year-old patient and his mother, both having significant phenotypic overlap with the initially reported patient. All 3 patients have distinct facial features (including mild hypotelorism and subtle mandibular asymmetry), developmental delay, and complex behavioral difficulties. A genotype-phenotype correlation narrows the shared phenotype to a common COL25A1 gene aberration and proposes that the concurrent EGF gene loss has a significant impact on the phenotypic severity. Overall, our patients provide data to support the existence of a novel 4q25 proximal deletion syndrome.

show abstract

Genome‐wide association analysis of age at onset in schizophrenia in a European‐American sample

Cited by 29 publications

References 86 publications

Molecular Identification of Hydroxylysine Kinase and of Ammoniophospholyases Acting on 5-Phosphohydroxy-l-lysine and Phosphoethanolamine

Molecular Identification of Hydroxylysine Kinase and of Ammoniophospholyases Acting on 5-Phosphohydroxy-l-lysine and Phosphoethanolamine

Genetic modifiers and subtypes in schizophrenia: Investigations of age at onset, severity, sex and family history

A Rare Recurrent 4q25 Proximal Deletion Not Involving the PITX2 Gene: A Genomic Disorder Distinct from Axenfeld-Rieger Syndrome

Contact Info

Product

Resources

About