title: Genome-scan for bipolar disorder with sib-pair families in the Sardinian population: a new susceptibility locus on chromosome 1p22-p21?
abstract: The discovery of the genetic factors implicated in the predisposition to complex diseases may greatly profit from genetic studies in isolated populations. In this perspective, we performed a genome-wide scan using 507 microsatellite markers, with an average interval size of 7.6 cM, on a sample of 88 nuclear families with at least two affected sibs with bipolar disorder recruited in the Sardinian population. 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.
authors.affiliation: Center of Clinical Psychopharmacology, Department of Neurosciences B.B. Brodie, University of Cagliari, Via Ospedale 46, Cagliari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Del Zompo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Severino
authors.forename: Raffaella
authors.initials: R
authors.lastname: Ardau
authors.forename: Caterina
authors.initials: C
authors.lastname: Chillotti
authors.forename: Mariapaola
authors.initials: M
authors.lastname: Piccardi
authors.forename: Colette
authors.initials: C
authors.lastname: Dib
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Muzard
authors.forename: Stéphane
authors.initials: S
authors.lastname: Soubigou
authors.forename: Murielle
authors.initials: M
authors.lastname: Derock
authors.forename: Raphaël
authors.initials: R
authors.lastname: Fournel
authors.forename: Yves
authors.initials: Y
authors.lastname: Vaubien
authors.forename: Sandrine
authors.initials: S
authors.lastname: Roche
authors.forename: Laurent
authors.initials: L
authors.lastname: Bowen-Squires
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Génin
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Cousin
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Deleuze
authors.forename: Nicole Faucon
authors.initials: NF
authors.lastname: Biguet
authors.forename: Jacques
authors.initials: J
authors.lastname: Mallet
authors.forename: Rolando
authors.initials: R
authors.lastname: Meloni
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D007558:Italy; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D035781:Siblings