BDgene

Core Gene from Gene Prioritization Pathways from PBA (Pathway-based Analysis) Enriched Pathways for Core Genes Enriched Pathways for Cross-disorder Genes

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Basic Info

Reference	Greenwood, T. A.,2012 PMID: 22329474
Citation	Greenwood, T. A., C. M. Nievergelt, et al. (2012). "Further evidence for linkage of bipolar disorder to chromosomes 6 and 17 in a new independent pedigree series." Bipolar Disord 14(1): 71-79.
Disease Type	Bipolar Disorder
Study Design	pedigree
Study Type	Genome-wide Linkage Study
Sample Size	229 individuals from 34 families
SNP/Region/Marker Size	whole genome wide with 440 markers
Predominant Ethnicity
Population	American and Canadian

Detail Info

Sample Diagnosis	DSM
Sample Status	Families were ascertained from the general North American population through both a systematic survey of clinical facilities, and through advertising and patient support groups from three sites: (i) San Diego, CA, USA; (ii) Vancouver, BC, Canada; and(iii) Cincinnati, OH, USA. Families were ascertained through a proband with bipolar disorder I or II and included if at least two additional members had either BD or recurrent major depressive disorder(MDD). We purposely chose broad criteria for ascertainment to better reflect families with BD in the population. Following informed consent procedures approved by the local institutional review boards (IRB) of the collaborative sites, the proband and all participating family members were interviewed directly using the Structured Clinical Interview for DSM-III-R (SCID) (12). Bipolar II disorder was diagnosed as BD not otherwise specified, modified so as to require a minimum duration of two days for hypomania.
Technique	Genotyping
Statistical Method	All analyses were performed under two diagnostic models of affection: (i) a narrow model (BD) that included diagnoses of bipolar I disorder, bipolar II disorder, and schizoaffective disorder (bipolar type); and (ii) a broad model (BD+MDD)that included a diagnosis from the narrow model plus a diagnosis of recurrent MDD.Initial analyses were performed using model-free, nonparametric two-point, and multipoint linkage analyses methods in Merlin to analyze the extent of allele sharing among all affected relative pairs (16). Marker allele frequencies were estimated among all individuals, the default in Merlin. Logarithm of odds (LOD) scores and corresponding p-values were converted from nonparametric scores using the Kong-and-Cox function (19) and were computed for each marker for two-point analyses. For the multipoint analyses,LOD scores and p-values were computed at a 1-cM interval across the chromosome, beginning with the first marker.
Result Summary	Initial nonparametric analyses of chromosomes 6 and 17 provided evidence for a modest replication of linkage to these chromosomes previously reported in other studies. Additional analyses using multipoint parametric methods provided further evidence to support the 6q25 region with a heterogeneity logarithm of odds score of 3.28. Evidence from two-point parametric analyses also provides a modest replication of our previous findings of linkage to the 23 cM region of chromosome 22q13 in our original University of California, San Diego sample of 20 families and 57 families from the National Institute of Mental Health bipolar disorder sample. CONCLUSIONS: Our results suggest replication of some reported linkage peaks, such as 6q25 and 17p12; however, other peaks from our own previous study, such as 5p15, 13q32, and 22q13, were either not replicated or were only modestly replicated in these analyses.

Regions reported by this study for BD (count: 18)

Region	Statistical Values	Author Comments	Result Category
8q24	Linkage analysis: for BD+MDD, LOD = 1.17	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
9q31	Linkage analysis: for BD, LOD = 1.91	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
Xq25	Linkage analysis: for BD+MDD, LOD = 1.45, MLOD = 1.21	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
6q16	Linkage analysis: for BD, MLOD = 1.61	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
4p16	Linkage analysis: for BD+MDD, MLOD = 1.46	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
7q21	Linkage analysis: for BD, LOD = 1.27	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
6q25	Linkage analysis: for BD+MDD, LOD = 1.03, MLOD = 1.51, HOLD = 3.28	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
20q11	Linkage analysis: for BD, LOD = 1.27, MLOD = 2.01	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
1q23	Linkage analysis: for BD, LOD = 1.67	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
2q35	Linkage analysis: for BD, MLOD = 1.35	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
22q11	Linkage analysis: for BD, LOD = 1.21, for BD+MDD, LOD = 1.4	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
17p12	Linkage analysis: for BD, LOD = 1.27, MLOD = 2.12	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
16q22	Linkage analysis: for BD, LOD = 1.13	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
17q21	Linkage analysis: for BD, MLOD = 1.39	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
17p13	Linkage analysis: for BD, LOD = 1.64	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
13q32	Linkage analysis: for BD+MDD, LOD = 1.28	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
15q21	Linkage analysis: for BD, MLOD = 1.85, for BD+MDD, MLOD = 1.78	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
14q22	Linkage analysis: for BD, MLOD = 1.22	No significant linkage was found in this region. No significant linkage was found in this region.	Negative