| 1 | Biol. Psychiatry 2007 Mar 61: 797-805 |
|---|---|
| PMID | 16996484 |
| Title | Haplotype analysis and a novel allele-sharing method refines a chromosome 4p locus linked to bipolar affective disorder. |
| Abstract | Bipolar affective disorder (BPAD) and schizophrenia (SCZ) are common conditions. Their causes are unknown, but they include a substantial genetic component. Previously, we described significant linkage of BPAD to a chromosome 4p locus within a large pedigree (F22). Others subsequently have found evidence for linkage of BPAD and SCZ to this region. We constructed high-resolution haplotypes for four linked families, calculated logarithm of the odds (LOD) scores, and developed a novel method to assess the extent of allele sharing within genes between the families. We describe an increase in the F22 LOD score for this region. Definition and comparison of the linked haplotypes allowed us to prioritize two subregions of 3.8 and 4.4 Mb. Analysis of the extent of allele sharing within these subregions identified 200 kb that shows increased allele sharing between families. Linkage of BPAD to chromosome 4p has been strengthened. Haplotype analysis in the additional linked families refined the 20-Mb linkage region. Development of a novel allele-sharing method allowed us to bridge the gap between conventional linkage and association studies. Description of a 200-kb region of increased allele sharing prioritizes this region, which contains two functional candidate genes for BPAD, SLC2A9, and WDR1, for subsequent studies. |
| SCZ Keywords | schizophrenia |
| 2 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2011 Sep 156B: 671-80 |
| PMID | 21688384 |
| Title | Genome-wide association analysis of age at onset in schizophrenia in a European-American sample. |
| Abstract | We performed a genome-wide association analysis to identify genetic variants influencing age at onset (AAO) and examine gene × gender interactions for AAO in schizophrenia (SCZ) using a European-American sample (1,162 cases). Linear regression model in PLINK was used to test for associations with AAO while the GxE option was chosen to test for the influence of gene × gender interactions. The most significant association with AAO was observed with SNP rs7819815 (P = 3.10×10(-7)) at 8q24.22. The next best signal was at 4q25 in COL25A1 gene (rs17039583, P = 4.30×10(-6)) and the third region was at 4p16.1 (rs17407555, P = 4.56×10(-6) , near RAF1P1, and rs4697924, P = 1.23×10(-5) within WDR1 gene). Conditional analysis on chromosome 4 indicated that 4p16.1 and 4q25 loci were independent. Furthermore, 2 SNPs (rs16834822 and rs16834824) at 1q43 in RYR2 showed strong associations in the female sample (P = 2.10×10(-6) and 2.33×10(-6) , respectively) and strong gene × gender interactions in influencing AAO (P = 9.23×10(-7) and 1.15×10(-6) , respectively) while the second best region showing gene × gender interaction was at 7q22.3 (rs179863, P = 2.33×10(-6) ). Using an independent sample of 1,068 cases, we could not replicate the associations for above top SNPs; however, we found nominal significance associations for their flanking SNPs (P < 0.05). These findings provide evidence of several genetic variants influencing AAO of SCZ. |
| SCZ Keywords | schizophrenia |