Study Report

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Basic Info

Reference	Del Zompo, M.,2010 PMID: 20468074
Citation	Del Zompo, M., G. Severino, et al. (2010). "Genome-scan for bipolar disorder with sib-pair families in the Sardinian population: a new susceptibility locus on chromosome 1p22-p21?" Am J Med Genet B Neuropsychiatr Genet 153B(6): 1200-1208.
Disease Type	Bipolar Disorder
Study Design	affected sib pairs
Study Type	Genome-wide linkage study
Sample Size	The sib-pair collection consisted of 88 nuclear families with a total of 381 individuals(210 affected individuals)
SNP/Region/Marker Size	507 microsatellite polymorphic markers for whole genome wide
Predominant Ethnicity	Caucasian
Population	Sardinian
Gender	95 males and 115 females
Age Group	Adults : The mean age at onset of mood disorder for the 210 bipolar patients was 24.3 years (SD=9 years) and the mean age at interview was 39.4 years (SD=15.5 years)

Detail Info

Sample Diagnosis	DSM
Sample Status	A total of 88 families with at least two sibs with BD were included in the genetic analyses from the Clinical Psychopharmacology Center(CPC) of the Section of Clinical Pharmacology, Department of Neuroscience, University of Cagliari and other Public Mental Health Centers located in different areas of Sardinia.The sib-pair collection consisted of 88 nuclear families with a total of 381 individuals. The diagnosis of BD was established for 210 affected individuals of whom 169 are BDI and 41 BDII. When one or both parentswere not available, as many as possible of the affected aswell as non-affected members of the sib-ship were recruited. In this study, all the families have at least two affected sibs, 39 families present only one parent and 9 families had both parents missing. More than half of the sib-pairs have been recruited in the same catchment area corresponding to the region of Cagliari while the others originate from the rest of Sardinia. Patients showing co-morbidity for alcohol and/or drug abuse were not recruited for the study.
Technique	genotyping
Statistical Method	Multipoint nonparametric linkage analysis was performed using the program GENEHUNTER 1.1 assuming equal allele frequencies at each marker. Further analyses were conducted using re-estimated allele frequencies (maximum likelihood estimation) calculated with MERLIN for the genome scan and the additional markers in the chromosome 1p22-p21 region.We used three standard diagnostic models for affection status: BP1 (manic syndromes,mostly bipolar I disorder), BP2 (BP1 plus bipolar II disorder with major depression) and BP3 (BP2 plus recurrent major depressive disorders). Individuals considered unaffected under any of these models (mainly never mentally ill) were coded as unknown in the statistical analyses.
Result Summary	An initial analysis yielded non-parametric linkage exceeding 3.4 with P-values <0.0003 at two adjacent markers, D1S206 and D1S435 in the 1p22-p21 chromosomal region. Moreover, positive linkage ranging between 2.0 and 3.0 was obtained for other loci in several cases in regions that have already been linked to predisposition to bipolar disorder, such as 5p15.33, 8q24.13, and 11q14.3. A subsequent analysis of the 1p22-p21 region using the same set of families and a dense panel of 20 new microsatellite markers, spaced at 1.2 cM on average, reinforced the finding of suggestive linkage for this region. Interestingly, NPL values above 2.1 and P-values <0.02 were obtained for a cluster of 10 markers comprising D1S435. Thus, this study suggests that the 1p22-p21 region may contain a new locus participating to the genetic susceptibility to bipolar disorder and reproduces positive linkage for several other loci already implicated in this pathology. Since the Sardinian population presents a peculiar genetic homogeneity, these results may pave the way to further studies for replication in this population contributing to the rapid discovery of the genetic factors predisposing to bipolar disorder.

Regions reported by this study for BD (count: 34)

Region	Statistical Values	Author Comments	Result Category
1p36.21	Linkage Analysis: For marker D1S228, NPL score = 2.25879, P-value = 0.01214; For marker D1S436, NPL score = 2.36298, P-value = 0.00923	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
1p34.2	Linkage Analysis: NPL score = 2.043, P-value = 0.02078	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
1p36.31	Linkage Analysis: NPL score = 2.60282, P-value = 0.00473	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
1p36.22	Linkage Analysis: NPL score = 2.01252, P-value = 0.02235	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
1p22-p21	Linkage Analysis: For marker D1S2793, Equal allele frequencies, NPL score = 2.75, P-value = 0.003; Estimated allele frequencies, NPL score = 2.36, P-value = 0.009	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
1p22.2	Linkage Analysis: NPL score = 3.42814, P-value = 0.00032	Significant linkage was found in this region. Significant linkage was found in this region.	Positive
1p33	Linkage Analysis: NPL score = 2.3339, P-value = 0.00997	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
1p32.2	Linkage Analysis: NPL score = 2.60703, P-value = 0.00467	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
2q24.3	Linkage Analysis: NPL score = 2.05156, P-value = 0.01979	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
2q22.3	Linkage Analysis: NPL score = 2.18092, P-value = 0.01436	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
7p14.2	Linkage Analysis: NPL score = 2.15851, P-value = 0.01567	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
5p15.33	Linkage Analysis: NPL score = 2.25038(1.66), P-value = 0.01201	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
1p36.33	Linkage Analysis: NPL score = 2.09451, P-value = 0.01835	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
1p36.32	Linkage Analysis: NPL score = 2.47876, P-value = 0.00673	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
21q21.1	Linkage Analysis: NPL score = 2.00883(1.51), P-value = 0.02194	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
1q32.1	Linkage Analysis: NPL score = 2.51978, P-value = 0.00599	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
11q14.1	Linkage Analysis: NPL score = 2.47461, P-value = 0.00681	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
11q14.3	Linkage Analysis: NPL score = 2.51031(2.33), P-value = 0.00616	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
16q24.1	Linkage Analysis: NPL score = 2.04078(1.85), P-value = 0.02032	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
1p21.2	Linkage Analysis: NPL score = 3.50866(2.49), P-value = 0.00023	Significant linkage was found in this region. Significant linkage was found in this region.	Positive
10q26.3	Linkage Analysis: NPL score = 2.43616(2.01), P-value = 0.00757	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
11p15.5	Linkage Analysis: NPL score = 2.34521, P-value = 0.00968	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
11q13.4	Linkage Analysis: NPL score = 2.23179, P-value = 0.01302	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
7q34	Linkage Analysis: NPL score = 2.1596, P-value = 0.01563	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
7q36	Linkage Analysis: NPL score = 2.59491(2.32), P-value = 0.00484	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
7p14.3	Linkage Analysis: NPL score = 2.3711, P-value = 0.00903	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
7p21.3	Linkage Analysis: NPL score = 2.1522, P-value = 0.01591	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
8q24.11	Linkage Analysis: NPL score = 2.34738, P-value = 0.00962	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
8q24.13	Linkage Analysis: NPL score = 2.72344(2.37), P-value = 0.00331	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
7q36.3	Linkage Analysis: NPL score = 2.50411, P-value = 0.00627	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
8p23.1	Linkage Analysis: NPL score = 2.05526, P-value = 0.02018	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
Xq25	Linkage Analysis: NPL score = 2.05161(1.82), P-value = 0.01549	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
9p21.2	Linkage Analysis: NPL score = 2.08612, P-value = 0.01819	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
9q21.31	Linkage Analysis: NPL score = 2.23584(2.14), P-value = 0.01247	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend