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	Lambert, D.,2005 PMID: 15940300
Citation	Lambert, D., F. Middle, et al. (2005). "Stage 2 of the Wellcome Trust UK-Irish bipolar affective disorder sibling-pair genome screen: evidence for linkage on chromosomes 6q16-q21, 4q12-q21, 9p21, 10p14-p12 and 18q22." Mol Psychiatry 10(9): 831-841.
Disease Type	Bipolar Disorder
Study Design	pedigree
Study Type	Candidate-region linkage study
Sample Size	395 bipolar affected sibling pairs
SNP/Region/Marker Size	494 microsatellite markers for 17 regions
Predominant Ethnicity	Caucasian
Population	British
Age Group	The mean age of onset of mood disorder for the 464 BPI individuals was 24.9 years (SD=9.1 years), and the mean age at interview of all affected sibs was 47.3 years (SD=15.3 years).

Detail Info

Sample Diagnosis	DSM
Sample Status	The additional families and individuals within the full stage 2 sample were collected using identical ascertainment criteria and methodology to those used in our stage 1 sample.11 Nuclear families were ascertained in which the proband met the DSM-IV12 criteria for Bipolar I disorder (BPI), and at least one other sibling met the criteria for BPI, Schizoaffective Bipolar disorder (SA-BP), Bipolar II disorder (BPII), Bipolar disorder not otherwise specified (BP-NOS) or Recurrent Major Depressive Disorder (MDD-R). Families were recruited in the Republic of Ireland and United Kingdom through their respective mental health services, patient support groups and articles in the national media. Subjects from all, save three of these families, were Caucasian Europeans. The full stage 2 sample is closely similar to the stage 1 sample in terms of pedigree sizes, gender distribution, distribution of diagnoses and characteristics of illness. The composition of the additional sample (ie that added to the stage 1 sample to form the full stage 2 sample) is as follows: DSM-IV diagnoses of additional genotyped individuals: BPI: 176; BPII: 9; SABP: 4; BP-NOS: 4; MDD-R: 21.The stage 2 sample included a total of 218, 283, and 395 ASPs for the narrow, intermediate and broad diagnostic models,respectively.
Technique	genotyping
Statistical Method	SPLINK was used to undertake two-point linkage analyses.Multipoint affected sib pair linkage analyses were undertaken using MAPMAKER/SIBS27 for X-chromosome data and GENEHUNTER version 2.128 for autosomal data.The three nested diagnostic models were as follows: Narrow including BPI individuals only, Intermediate which included BPI, BPII and SA-BP, and the Broad diagnostic model which included, additional to those in the intermediate category, individuals with BP-NOS and those with MDD-R.
Result Summary	Under the broad diagnostic model, two markers gave LOD scores exceeding 3 with two-point analysis: D4S392 (LOD=3.30) and D10S197 (LOD=3.18). Multipoint analysis demonstrated suggestive evidence of linkage between BPAD and chromosomal regions 6q16-q21 (MLS=2.61) and 4q12-q21 (MLS=2.38). 6q16-q21 is of particular interest because our data, together with those from two recent genome scans, make this the best supported linkage region in BPAD. Further, our data show evidence of a gender effect at this locus with increased sharing predominantly within the male-male pairs. Our scan also provides support for linkage (MLS> or =1.5) at several other regions that have been implicated in meta-analyses of bipolar disorder and/or schizophrenia including 9p21, 10p14-p12 and 18q22.

Regions reported by this study for BD (count: 14)

Region	Statistical Values	Author Comments	Result Category
10p12	Linkage analysis: For marker D10S197, Two point LOD score = 1.55(narrow), 2.45(intermediate), 3.18(broad); For marker D10S548, Multipoint MLS = 1.12(narrow), 0.62(intermediate), 0.46(broad); Two point LOD score = 0.73(narrow), 0.04(intermediate), 0.03(broad);	Suggestive linkage was found in this region at D10S197. Suggestive linkage was found in this region at D10S197.	Trend
10p14	Linkage analysis: Multipoint MLS = 1.56(narrow), 1.13(intermediate), 0.31(broad); Two point LOD score = 1.03(narrow), 0.16(intermediate), 0.05(broad);	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
18q12	Linkage analysis: Multipoint MLS = 1.35(narrow), 0.21(intermediate), 0.12(broad); Two point LOD score = 0.23(narrow), 0(intermediate), 0(broad);	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
18q22	Linkage analysis: For marker D18S48, Multipoint MLS = 1.46(narrow), 0.47(intermediate), 0.59(broad); Two point LOD score = 0.79(narrow), 0.22(intermediate), 0.22(broad); For marker D18S474, Two point LOD score = 0.55(narrow), 0.04(intermediate), 0(broad)	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
2q37-2qter	Linkage analysis: Multipoint MLS = 1.14(narrow), 2.08(intermediate), 1.87(broad); Two point LOD score = 2.11(narrow), 2.52(intermediate), 2.25(broad);	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
4p14-p13	Linkage analysis: Multipoint MLS = 0.58(narrow), 1.61(intermediate), 1.76(broad); Two point LOD score = 0.96(narrow), 2.32(intermediate), 2.17(broad);	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
4q12-q21	Linkage analysis: Multipoint MLS = 1.82(narrow), 2.24(intermediate), 2.38(broad); Two point LOD score = 2.16(narrow), 2.64(intermediate), 3.3(broad);	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
4q26-q28	Linkage analysis: For marker D4S402, Two point LOD score = 1.67(narrow), 1.94(intermediate), 1.73(broad);	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
Xq21-q22	Linkage analysis: Multipoint MLS = 0.89(narrow), 1.97(intermediate), 1(broad); Two point LOD score = 1.03(narrow), 1.8(intermediate), 0.66(broad);	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
9p21-p12	Linkage analysis: For marker D9S319, Two point LOD score = 1.93(narrow), 2.02(intermediate), 1.39(broad);	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
7q21	Linkage analysis: Multipoint MLS = 1.35(narrow), 1.07(intermediate), 0.72(broad); Two point LOD score = 1.95(narrow), 2.03(intermediate), 1.47(broad);	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
7q11.2	Linkage analysis: Multipoint MLS = 1.2(narrow), 0.7(intermediate), 0.92(broad); Two point LOD score = 1.26(narrow), 1.21(intermediate), 1.45(broad);	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
6q16-q21	Linkage analysis: Multipoint MLS = 1.34(narrow), 1.43(intermediate), 2.61(broad); Two point LOD score = 1.06(narrow), 0.99(intermediate), 2.62(broad);	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
6p12-q13	Linkage analysis: Multipoint MLS = 1.26(narrow), 0.65(intermediate), 0.27(broad); Two point LOD score = 1.9(narrow), 1.24(intermediate), 0.73(broad);	No significant linkage was found in this region. No significant linkage was found in this region.	Negative