Study Report

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Basic Info

Reference	Marcheco-Teruel, B.,2006 PMID: 16917938
Citation	Marcheco-Teruel, B., T. J. Flint, et al. (2006). "A genome-wide linkage search for bipolar disorder susceptibility loci in a large and complex pedigree from the eastern part of Cuba." Am J Med Genet B Neuropsychiatr Genet 141B(8): 833-843.
Disease Type	Bipolar I Disorder
Study Design	pedigree
Study Type	Genome-wide linkage study
Sample Size	a six generation pedigree with 28 affected members
SNP/Region/Marker Size	10,043 SNP markers for whole genome wide
Predominant Ethnicity	Caucasian
Population	Cuban

Detail Info

Sample Diagnosis	DSM
Sample Status	One large and highly consanguineous six-generation family from a relatively isolated region in Velasco, in eastern Cuba, with multiple affected members, mostly of European Caucasian descent, was identified through bipolar probands in contact with the psychiatric hospitals in Gibara and Holguin in the period March 1999-March 2004. During this period 30 individuals were diagnosed with affective disorders. In the family, no male-to-male transmission of the disease was observed. For the family members, the following inclusion criteria were applied: (1) Diagnosis using DSM-IV [American Psychiatric Association, 1994] and ICD-10 DCR [World Health Organization, 1993], as bipolar I disorder (BP I) or recurrent depressive disorder (RD). (2) A positive family history in first- or second-degree relatives for an affective disorder. Individuals with primary alcohol dependence, and their descendants, were excluded from the study.
Technique	genotyping
Statistical Method	We performed parametric and non-parametric linkage analyses using the GENEHUNTER software package, version 2.1r5 [Kruglyak et al., 1996].Model 1 (broad) included individuals affected with bipolar I disorder or recurrent depressive disorder. Model 2 (narrow) included individuals affected with bipolar I disorder only.
Result Summary	For the entire family a suggestive parametric LOD score was obtained under the dominant model and the broader phenotype at 14q11.2-12 (LOD = 2.05). In the same region, a non-parametric LOD score close to genome-wide significance was also obtained, based on the entire family (NPL = 7.31, P-value = 0.07). For two individual branches of the pedigree, genome-wide significance (P < 0.005) was obtained with NPL scores of 8.71 and 12.99, respectively, also in the same region on chromosome 14. Chromosome 5q21.3-22.3 also showed close to genome-wide significant linkage for the complete pedigree (NPL = 7.26, P = 0.07), also supported by significant linkage in one individual branch (NPL = 9.86, P < 0.005). In addition, genome-wide significant nonparametric results (P-values <0.005) were obtained for individual branches at 5p13.1-q12.3, 6p22.3, 8q13.3-21.13, and 10q22.3-23.32. Finally, 2p25.1-25.3, 2p13.3-14, 3p14.2, 6p22.3-24.1, 7p14.1-14.2, 8q12.2-12.3, 10q21.1-21.2, 14q13.1-21.1, 15q15.1-21.2, and 22q12.3-13.32 showed suggestive linkage in the complete family. Most of these potential susceptibility loci overlap with, or are close, to previous linkage findings. The locus on 5q may, however, represent a novel susceptibility locus.

Regions reported by this study for BD (count: 29)

Region	Statistical Values	Author Comments	Result Category
10q21.1-2	Linkage analyses: LOD(rec) = 1.08, LOD(dom) = 1.18, NPL = 6.95, Locus specific GH P-value = 0.005, Empirical P-value = 0.28 for Family 1a	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
10q22.3-23.32	Linkage analyses: LOD(rec) = 1.11, LOD(dom) = 1.35, NPL = 9.91, Locus specific GH P-value = 0.005, Empirical P-value =< 0.005 for Family 1a	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
15q21.3	Linkage analyses: LOD(rec) = 0.17, LOD(dom) = 0.62, NPL = 4.43, Locus specific GH P-value = 0.007, Empirical P-value = 0.96 for Family 1	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
15q15.1-21.2	Linkage analyses: LOD(rec, Model1) = 0.71, LOD(rec, Model2) = 2.07, LOD(doc, Model1) = 1.53, NPL(Model2) = 1.87, Locus specific GH P-value(Model1) = 0.034, Empirical P-value(Model1) = 1 for the Complete Family	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
14q13.2-21.3	Linkage analyses: LOD(rec) = 0.11, LOD(dom) = 1.32, NPL = 8.71, Locus specific GH P-value = 0.005, Empirical P-value =< 0.005 for Family 1a	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
14q13.1-21.1	Linkage analyses: LOD(rec, Model1) = -3.66, LOD(rec, Model2) = -2.52, LOD(doc, Model1) = 1.52, NPL(Model2) = 5.55, Locus specific GH P-value(Model1) = 0.008, Empirical P-value(Model1) = 0.61 for the Complete Family	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
14q11.2-14q12	Linkage analyses: LOD(rec, Model1) = 1.03, LOD(rec, Model2) = 1.13, LOD(doc, Model1) = 2.05, NPL(Model2) = 7.31, Locus specific GH P-value(Model1) = 0.001, Empirical P-value(Model1) = 0.07 for the Complete Family	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
14q11.2-12.0	Linkage analyses: LOD(rec) = 1.08, LOD(dom) = 1.41, NPL = 12.99, Locus specific GH P-value = 0.002, Empirical P-value =< 0.005 for Family 2	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
11q14.1-14.3	Linkage analyses: LOD(rec) = 1.11, LOD(dom) = 1.03, NPL = 5.88, Locus specific GH P-value = 0.004, Empirical P-value = 0.85 for Family 3	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
10q22.3-24.1	Linkage analyses: LOD(rec, Model1) = -0.67, LOD(rec, Model2) = -1.58, LOD(doc, Model1) = 0.6, NPL(Model2) = 4.67, Locus specific GH P-value(Model1) = 0.014, Empirical P-value(Model1) = 0.77 for the Complete Family	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
2p25.3-25.1	Linkage analyses: LOD(rec) = 0.18, LOD(dom) = 1.01, NPL = 9.36, Locus specific GH P-value = 0.003, Empirical P-value = 0.32 for Family 3	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
2p25.1-25.3	Linkage analyses: LOD(rec, Model1) = -0.76, LOD(rec, Model2) = -0.88, LOD(doc, Model1) = 0.31, NPL(Model2) = 4.41, Locus specific GH P-value(Model1) = 0.015, Empirical P-value(Model1) = 0.84 for the Complete Family	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
2p14-13.3	Linkage analyses: LOD(rec) = 1.33, LOD(dom) = 0.1, NPL = 7, Locus specific GH P-value = 0.006, Empirical P-value = 0.98 for Family 1	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
22q12.3-13.32	Linkage analyses: LOD(rec) = 0.16, LOD(dom) = 1.25, NPL = 7.29, Locus specific GH P-value = 0.005, Empirical P-value = 0.24 for Family 1a	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
20p12.2-12.1	Linkage analyses: LOD(rec) = 0.09, LOD(dom) = 1.08, NPL = 4.75, Locus specific GH P-value = 0.005, Empirical P-value = 0.91 for Family 1a	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
1q32.3-41	Linkage analyses: LOD(rec) = 0.1, LOD(dom) = 1.12, NPL = 5.33, Locus specific GH P-value = 0.005, Empirical P-value = 0.88 for Family 1a	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
16q12.2-23.1	Linkage analyses: LOD(rec) = 2.03, LOD(dom) = 0.11, NPL = 0.32, Locus specific GH P-value = 0.139, Empirical P-value = 1 for Family 2	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
15q24.1-25.2	Linkage analyses: LOD(rec) = 1.14, LOD(dom) = 1.03, NPL = 5.85, Locus specific GH P-value = 0.005, Empirical P-value = 0.85 for Family 3	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
3p14.2	Linkage analyses: LOD(rec, Model1) = 2.31, LOD(rec, Model2) = 1.43, LOD(doc, Model1) = 1.05, NPL(Model2) = 1.31, Locus specific GH P-value(Model1) = 0.063, Empirical P-value(Model1) = 1 for the Complete Family	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
4q31.22-34.1	Linkage analyses: LOD(rec) = 2.03, LOD(dom) = 0.05, NPL = 1.04, Locus specific GH P-value = 0.036, Empirical P-value = 1 for Family 2	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
5p13.1-5q12.3	Linkage analyses: LOD(rec) = 0.14, LOD(dom) = 1.42, NPL = 12.96, Locus specific GH P-value = 0.002, Empirical P-value =< 0.005 for Family 2	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
5q21.3-22.3	Linkage analyses: LOD(rec) = 1.11, LOD(dom) = 1.42, NPL = 13.74, Locus specific GH P-value = 0, Empirical P-value =< 0.005 for Family 2	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
6p22.3	Linkage analyses: LOD(rec) = 1.02, LOD(dom) = 1.35, NPL = 9.86, Locus specific GH P-value = 0.005, Empirical P-value =< 0.005 for Family 1a	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
6p22.3-24.1	Linkage analyses: LOD(rec, Model1) = -0.48, LOD(rec, Model2) = 0.24, LOD(doc, Model1) = 1.58, NPL(Model2) = 4.88, Locus specific GH P-value(Model1) = 0.013, Empirical P-value(Model1) = 0.75 for the Complete Family	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
7p14.1-2	Linkage analyses: LOD(rec, Model1) = 2.8, LOD(rec, Model2) = 2.71, LOD(doc, Model1) = 0.87, NPL(Model2) = 1.51, Locus specific GH P-value(Model1) = 0.049, Empirical P-value(Model1) = 1 for the Complete Family	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
8q12.2-12.3	Linkage analyses: LOD(rec) = 0.04, LOD(dom) = 0.69, NPL = 2.6, Locus specific GH P-value = 0.025, Empirical P-value = 1 for Family 1a; LOD(rec) = 1.25, LOD(dom) = 1.03, NPL = 5.93, Locus specific GH P-value = 0.004, Empirical P-value = 0.85 for Family 3	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
8q12.2-3	Linkage analyses: LOD(rec, Model1) = -0.44, LOD(rec, Model2) = -1.66, LOD(doc, Model1) = 0.53, NPL(Model2) = 3.86, Locus specific GH P-value(Model1) = 0.016, Empirical P-value(Model1) = 0.94 for the Complete Family	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
8q13.3-21.13	Linkage analyses: LOD(rec) = 0.11, LOD(dom) = 1.23, NPL = 7.7, Locus specific GH P-value = 0.005, Empirical P-value = 0.04 for Family 1a	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
9q33.3-34.3	Linkage analyses: LOD(rec) = 0.7, LOD(dom) = 1.04, NPL = 4.5, Locus specific GH P-value = 0.005, Empirical P-value = 0.92 for Family 1a	No significant linkage was found in this region. No significant linkage was found in this region.	Negative