Preliminary evidence for linkage to chromosome 1q31‐32, 10q23.3, and 16p13.3 in a South African cohort with bipolar disorder

Savitz, Jonathan; Cupido, Cinda-Lee; Ramesar, Raj

doi:10.1002/ajmg.b.30461

Cited by 9 publications

(10 citation statements)

References 46 publications

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“…The loci on 1p13–31 and 1q25–31 implicated here have also both been reported to be involved in BP susceptibility [23,45,46,47,48,49,50]. The chromosome 1p13–31 region had been highlighted by our initial genome scan [10], and the present study has further strengthened this signal.…”

Section: Discussionsupporting

confidence: 79%

Genome-Wide Linkage Scan of Bipolar Disorder in a Colombian Population Isolate Replicates Loci on Chromosomes 7p21–22, 1p31, 16p12 and 21q21–22 and Identifies a Novel Locus on Chromosome 12q

et al. 2010

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Background/Aims: Bipolar disorder (BP) is a severe psychiatric illness, characterised by alternating episodes of depression and mania, which ranks among the top ten causes of morbidity and life-long disability world-wide. We have previously performed a whole-genome linkage scan on 6 pedigrees segregating severe BP from the well-characterised population isolate of Antioquia, Colombia. We recently collected genotypes for the same set of 382 autosomal microsatellite markers in 9 additional Antioquian BP pedigrees. Here, we report the analysis of the combined pedigree set. Methods: Linkage analysis using both parametric and nonparametric approaches was conducted for 3 different diagnostic models: severe BP only (BPI); mood disorders (BPI, BPII and major depression); and psychosis (operationally defined by the occurrence of at least 1 episode of hallucinations and/or delusions). Results and Conclusion: For BPI only, the most interesting result was obtained for chromosome 7p21.1–p22.2 under a recessive model of inheritance (heterogeneity LOD score = 2.80), a region that had previously been linked to BP in a study on Portuguese Island families. For both BPI and mood disorders, nonparametric analyses identified a locus on chromosome 12ct–q14 (nonparametric linkage = 2.55 and 2.35, respectively). This locus has not previously been reported as a candidate region for BP. Additional candidate regions were found on chromosomes 1p22–31 (mood disorders) and 21q21–22 (BPI), 2 loci that have repeatedly been implicated in BP susceptibility. Linkage analysis of psychosis as a phenotype identified candidate regions on chromosomes 2q24–31 and 16p12–q12. The finding on chromosome 16p is noteworthy because the same locus has been implicated by genome-wide association analyses of BP.

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Section: Discussionsupporting

confidence: 79%

Genome-Wide Linkage Scan of Bipolar Disorder in a Colombian Population Isolate Replicates Loci on Chromosomes 7p21–22, 1p31, 16p12 and 21q21–22 and Identifies a Novel Locus on Chromosome 12q

et al. 2010

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“…The search was performed in pub med for every chromosome separately with the key words: “Bipolar disorder, genetics, linkage, chromosome 1…X” and “Migraine, genetics, linkage, chromosome 1…X”, Table 3 displays all linkage loci that have been significantly or suggestively found in migraine linkage studies (Gardner et al, 1997; Nyholt et al, 1998a,b, 2000; Jones et al, 2001; Carlsson et al, 2002; Wessman et al, 2002; Lea et al, 2002; Björnsson et al, 2003; Soragna et al, 2003; Cader et al, 2003; Nyholt et al, 2005; Russo et al, 2005; Lea et al, 2005; Anttila et al, 2006), and the bipolar linkage studies (Savitz et al, 2007; Jamra et al, 2007; Zandi et al, 2007; Goes et al, 2007; Cassidy et al, 2007; Kerner et al, 2007; Jones et al, 2007; Etain et al, 2006; Marcheco-Teruel et al, 2006; Tomàs et al, 2006; Mukherjee et al, 2006; Schumacher et al, 2005; Hamshere et al, 2005; Lambert et al, 2005; McQueen et al, 2005; Kealey et al, 2005; Lin et al, 2005; Macgregor et al, 2004; Middleton et al, 2004; Fallin et al, 2004; Curtis et al, 2003; McInnis et al, 2003; Willour et al, 2003; Ewald et al, 2003; Ekholm et al, 2003; Ewald et al, 2002; Ekholm et al, 2002; Bailer et al, 2002; Dick et al, 2002; Cichon et al, 2001; Kelsoe et al, 2001; Radhakrishna et al, 2001; Detera-Wadleigh et al, 1999; Morissette et al, 1999; Ginns et al, 1998; Ewald et al, 1998; Detera-Wadleigh et al, 1997; Edenberg et al, 1997; Blackwood et al, 1996; Turecki et al, 1995; Pekkarinen et al, 1995) that have demonstrated overlapping or closely related linkage to these migraine loci. In addition we compared linkage studies in BPAD to the identified genes in FHM, and the BPAD (Jamra et al, 2007; Zandi et al, 2007; Hamshere et al, 2005; Middleton et al, 2004; Fallin et al, 2004; …”

Section: Discussionmentioning

confidence: 99%

A genome-wide linkage study of bipolar disorder and co-morbid migraine: Replication of migraine linkage on chromosome 4q24, and suggestion of an overlapping susceptibility region for both disorders on chromosome 20p11

Oedegaard

Greenwood

Lunde

et al. 2010

Journal of Affective Disorders

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Migraine and Bipolar Disorder (BPAD) are clinically heterogeneous disorders of the brain with a significant, but complex, genetic component. Epidemiological and clinical studies have demonstrated a high degree of co-morbidity between migraine and BPAD. Several genome-wide linkage studies in BPAD and migraine have shown overlapping regions of linkage on chromosomes, and two functionally similar voltage-dependent calcium channels CACNA1A and CACNA1C have been identified in familial hemiplegic migraine and recently implicated in two whole genome BPAD association studies, respectively. We hypothesized that using migraine co-morbidity to look at subsets of BPAD families in a genetic linkage analysis would prove useful in identifying genetic susceptibility regions in both of these disorders. We used BPAD with co-morbid migraine as an alternative phenotype definition in a re-analysis of the NIMH Bipolar Genetics Initiative wave 4 data set. In this analysis we selected only those families in which at least two members were diagnosed with migraine by a doctor according to patients' reports. Nonparametric linkage analysis performed on 31 families segregating both BPAD and migraine identified a linkage signal on chromosome 4q24 for migraine (but not BPAD) with a peak LOD of 2.26. This region has previously been implicated in two independent migraine linkage studies. In addition we identified a locus on chromosome 20p11 with overlapping elevated LOD scores for both migraine (LOD = 1.95) and BPAD (LOD = 1.67) phenotypes. This region has previously been implicated in two BPAD linkage studies, and, interestingly, it harbors a known potassium dependant sodium/calcium exchanger gene, SLC24A3, that plays a critical role in neuronal calcium homeostasis. Our findings replicate a previously identified migraine linkage locus on chromosome 4 (not co-segregating with BPAD) in a sample of BPAD families with co-morbid migraine, and suggest a susceptibility locus on chromosome 20, harboring a gene for the migraine/BPAD phenotype. Together these data suggest that some genes may predispose to both bipolar disorder and migraine.

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“…The maximum occurred at marker D16S410 located at $19 megabasepairs (Mb) on chromosome 16. Within only 2 Mb of D16S410, five other studies also found linkage signals with BP [Foroud et al, 2000;Dick et al, 2002;Middleton et al, 2004;Cheng et al, 2006;Service et al, 2006], and a few other studies reported evidence for linkage nearby in the 16p11, 16p12, and 16p13 regions [McInnes et al, 1996;Edenberg et al, 1997;Cichon et al, 2001;Ewald et al, 2002;Ekholm et al, 2003;McQueen et al, 2005;Savitz et al, 2007] (see Fig. 1).…”

mentioning

confidence: 85%

Replication of linkage with bipolar disorder on chromosome 16p in the eastern Quebec population

Mérette

Roy

Bureau

et al. 2008

American J of Med Genetics Pt B

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In a previous study [Maziade et al. (2005); Mol Psychiatry 10:486-499], we provided evidence for linkage (parametric lod score of 4.05) on chromosome 16p for bipolar affective disorder (BP) in 21 kindreds from Eastern Quebec, a population characterized by a founder effect. Using a stringent design, we performed a replication study in a second sample of 27 kindreds (sample 2) collected from the same population and assessed with the same methodologies as in our original sample (sample 1), that is with the same diagnostic procedure and using a common set of 23 markers studied with model-based (parametric) and model-free (nonparametric) linkage analyses. We replicated our initial finding with P values <0.001. Indeed, maximum NPL(all) scores of 3.7 and 3.52 were found at marker D16S3060 in sample 2 for the narrow and broad BP phenotype definition, respectively. For the latter definition, the nonparametric score reached 3.87 in the combined sample, a value that exceeded the maximum NPL score obtained in each individual sample (NPL(all) = 2.32 in sample 1; NPL(all) = 3.52 in sample 2). Moreover, a refined phenotype restricted to BP associated with psychosis yielded significant evidence for linkage in each individual sample (NPL(all) = 2.38 in sample 1; NPL(all) = 2.72) while yielding the best result (NPL(all) score = 3.90) in the combined sample (samples 1 and 2), despite an important reduction in the number of affected individuals. It is also noteworthy that the use of the refined phenotype provided a location of the maximum linkage peak shared by both samples, that is, at marker D16S668 in 16p13.12, suggesting consistency across samples. Our study provided one of the strongest pieces of evidence for linkage with BP in 16p and illustrated the heuristic potential of a replication study in a second sample ascertained from the same population and using homogeneous methodologies.

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Preliminary evidence for linkage to chromosome 1q31‐32, 10q23.3, and 16p13.3 in a South African cohort with bipolar disorder

Cited by 9 publications

References 46 publications

Genome-Wide Linkage Scan of Bipolar Disorder in a Colombian Population Isolate Replicates Loci on Chromosomes 7p21–22, 1p31, 16p12 and 21q21–22 and Identifies a Novel Locus on Chromosome 12q

Genome-Wide Linkage Scan of Bipolar Disorder in a Colombian Population Isolate Replicates Loci on Chromosomes 7p21–22, 1p31, 16p12 and 21q21–22 and Identifies a Novel Locus on Chromosome 12q

A genome-wide linkage study of bipolar disorder and co-morbid migraine: Replication of migraine linkage on chromosome 4q24, and suggestion of an overlapping susceptibility region for both disorders on chromosome 20p11

Replication of linkage with bipolar disorder on chromosome 16p in the eastern Quebec population

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