A genome-wide scan shows significant linkage between bipolar disorder and chromosome 12q24.3 and suggestive linkage to chromosomes 1p22–21, 4p16, 6q14–22, 10q26 and 16p13.3

Abstract

The present study reports a genomewide scan using linkage analysis for risk genes involved in bipolar disorder with 613 microsatellite markers including additional testing of promising regions. As previously published significant linkage was obtained at chromosome 12q24.3 with a two-point parametric lod score of 3.42 at D12S1639 including all members in both families (empirical P-value 0.00004, genome-wide P-value 0.0417). The multipoint parametric lod score at D12S1639 was 3.63 (genome-wide P-value 0.0265). At chromosome 1p22-p21 a parametric, affecteds-only two-point lod score of 2.75 at marker D1S216 was found (empirical Pvalue 0.0002, genome-wide P-value 0.1622). A three-point lod score of 2.98 (genome-wide Pvalue 0.1022) at D1S216, and a multipoint non-parametric analysis with a maximum NPL-all score of 17.60 (P-value 0.00079) at D1S216 further supported this finding. A number of additional loci on chromosomes 4p16, 6q14-q22, 10q26 and 16p13.3 yielded parametric lod scores around or above 2.

Genetic Linkage and Association Analysis for Loneliness in Dutch Twin and Sibling Pairs Points to a Region on Chromosome 12q23–24

“…The 12q23-q24 region was, however, not reported in meta-analyses of bipolar disorder (Segurado et al, 2003) or schizophrenia . Since the publication of the meta-analyses several further genome scans were published (see Table II) with at least 2 genome scans reporting genome wide significance (Ewald et al, 2002;Shink et al, 2005a, b) within the 12q23-24 region.…”

A neuronal nitric oxide synthase (NOS-I) haplotype associated with schizophrenia modifies prefrontal cortex function

“…All patients were inpatients at the Department of Psychiatry at least once. One hundred and ninety-five patients suffered from schizophrenic disorders according to ICD-10 criteria (56, Figure 1 Based on the chromosomal location built on Ensembl Freeze 04/04, Lod scores of markers on 12q24 are given; the investigated phenotype was either SCZ, [14][15][16][17][18]23 bipolar disorder [5][6][7][8][9][10][11][12]19,22 or major depression. 13 Highlighted are the loci for DAAO, suggested as a candidate gene for bipolar disorder and SCZ, ATP2A2 (the Darier's disease gene) and NOS1.…”

“…3,4 A further consistently identified locus for endogenous psychoses, usually with Lod scores between 2 and 3, is located on 12q22-24. BPD has been replicated 8 times, [5][6][7][8][9][10][11][12] but also major depression (MD) was linked to this locus with a very high Lod-score > 6, which might be due to the homogeneity of the sample consisting of 110 pedigrees from Utah. 13 SCZ and schizoaffective disorder [14][15][16][17] and the marker 'negative symptoms' in SCZ 18 linked to 12q22-24 as well.…”

Excitement and confusion on chromosome 6q: the challenges of neuropsychiatric genetics in microcosm

“…39 The second focus of findings (F-2) is at 105 Mb, mainly in BPD, with one significant study 42 and several supporting studies, 37,38,46 but also studies on SCZ, 24 autism 52 and multiple sclerosis. 53 The third focus (F-3) is for BPD and is located at 126 Mb with a very significant finding from one study of Portuguese pedigrees.…”

“…45 The fourth focus (F-4) is centered at 136 Mb, with significant findings in SCZ-related disorders coming from one linkage study 31,32 and one association study, 14 and weak support from other studies in SCZ. 26,39 Support for this focus also comes from linkage and association studies in BPD 38,48,49 and from a meta-analysis of linkage studies in BPD 5 as well as from the presence of AHI1, a gene causing a severe neuropsychiatric disorder (Joubert Syndrome) in this location. Weaker positive results in linkage studies of SCZ and BPD were also demonstrated distal to this focus 28,40,47 and may represent poorer localization of the same locus.…”