1. Data summary

1.1 BD genetic factors

BDgene contains multi-type BD-related genetic factors extracted from 918 studies. Category statistics of BD related genetic factors were shown in Table 1.

Table 1 Data content and statistics of BD related genetic factors in BDgene (by March 31, 2016)

1.2 BD shared genetic factors with SZ and MDD

The genetic studies that investigated the association of genetic factors with more than one disease in one study under identical or similar methodological conditions were regarded as 'cross-disorder studies'. Shared genetic factors between BD and SZ/MDD were obtained from the cross-disorder studies on two diseases (BD-SZ or BD-MDD) or three diseases (BD-SZ-MDD). Meanwhile, potential cross-disorder genes from intersection analysis of multi-disease candidate genes were also presented. Category statistics of BD shared genetic factors with SZ/MDD were shown in Table 2.

Table 2 Statistics of shared genetic factors of BD-SZ, BD-MDD and BD-SZ-MDD (by March 31 2016)

2. Data collection

2.1 Literature search

BDgene was established based on an integrated high-quality dataset derived from profound literature reading with manual curation. These publications for genetic susceptibility studies of BD were obtained via an extensive search in PubMed, including genome-wide association study, candidate-gene association study, linkage study, mutational study, copy number variation analysis and meta-analysis for association study or linkage study. The search terms are as below:

("bipolar" [Title/Abstract] OR "manic depressive" [Title/Abstract] OR "manic depression" [Title/Abstract]) AND (polymorphism [Title/Abstract] OR SNP [Title/Abstract] OR haplotype [Title/Abstract] OR interaction [Title/Abstract] OR variant [Title/Abstract] OR variation [Title/Abstract] OR mutation [Title/Abstract] OR CNV [Title/Abstract] OR "copy number variation" [Title/Abstract] OR repeats [Title/Abstract] OR deletion [Title/Abstract] OR duplication [Title/Abstract] OR ((gene [Title/Abstract] OR locus [Title/Abstract] OR chromosome [Title/Abstract] OR genetic [Title/Abstract] OR genome [Title/Abstract] OR genomic [Title/Abstract]) AND (linkage [Title/Abstract] OR associat* [Title/Abstract])))

2.2 Data extraction and categorization

Multi-type genetic factors were collected from literature, not only disease related SNP, gene, region, but also haplotype, gene-gene interaction, pathway, and other variants. To present a panoramic relation between genetic factors and disease, statistical results (e.g. P-values, ORs, LODs) were evaluated and detailed evidences (e.g. study design, sample population, analytical method) from original publications were presented. To better illustrate the association between genetic candidates and diseases, results were categorized into 'Positive', 'Negative' and 'Trend' according to the criteria described in Table 3. We also presented authors' original comments as an additional reference for the results evaluation.

3. Data analysis

4. Data update

Before the formal release of BDgene, BDgene has been updated three times, including Beta V1.0 (till June 30, 2012), Beta V2.0 (till October 31, 2012) and Beta V3.0 (till March 1, 2013). Since 2013, BDgene was updated quarterly. The version formula is V+year+q+number (e.g. V2013q1). But after several quarters' update, we found the increased papers for each update was only around 10. Then we decided to update BDgene every half year from the second half of 2014.

To show the latest publications on BD genetic study, newly published studies in the recently month will be downloaded automatically monthly from PubMed by using the search formula as shown above. Then, manual filtering is performed to remove the irrelevance. The papers after filtering are shown in the rolling window of "New Papers" on the home page, and the data extraction and analysis will be carried out in the next update.

1. Lander, E. and Kruglyak, L. (1995) Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet, 11, 241-247.
2. Chang S, Zhang W, Gao L, Wang J (2012): Prioritization of candidate genes for attention deficit hyperactivity disorder by computational analysis of multiple data sources. Protein & Cell. 3:526-534.
3. Serretti, A. and Mandelli, L. (2008) The genetics of bipolar disorder: genome 'hot regions,' genes, new potential candidates and future directions. Mol Psychiatry, 13, 742-771.
4. Ferreira MA, O'Donovan MC, Meng YA, Jones IR, Ruderfer DM, Jones L, et al. (2008): Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nature genetics. 40:1056-1058.
5. Liu Y, Blackwood DH, Caesar S, de Geus EJ, Farmer A, Ferreira MA, et al. (2011): Meta-analysis of genome-wide association data of bipolar disorder and major depressive disorder. Mol Psychiatry. 16:2-4. 6. Green EK, Hamshere M, Forty L, Gordon-Smith K, Fraser C, Russell E, et al. (2012): Replication of bipolar disorder susceptibility alleles and identification of two novel genome-wide significant associations in a new bipolar disorder case-control sample. Mol Psychiatry. 7. Chen YA, Tripathi LP, Mizuguchi K (2011): TargetMine, an integrated data warehouse for candidate gene prioritisation and target discovery. PLoS ONE. 6:e17844.
8. Zhang, K., Cui, S., Chang, S., Zhang, L. and Wang, J. (2010) i-GSEA4GWAS: a web server for identification of pathways/gene sets associated with traits by applying an improved gene set enrichment analysis to genome-wide association study. Nucleic acids research, 38, W90-95.
9. Allen NC, Bagade S, McQueen MB, Ioannidis JPA, Kavvoura FK, Khoury MJ, Tanzi RE, Bertram L (2008) Systematic Meta-Analyses and Field Synopsis of Genetic Association Studies in Schizophrenia: The SzGene Database. Nat Genet 40(7): 827-34.
10. Guo, L., Zhang, W., Chang, S., Zhang, L., Ott, J. and Wang, J. (2012) MK4MDD: A Multi-Level Knowledge Base and Analysis Platform for Major Depressive Disorder. PLoS ONE, 7, e46335.