Genome scan of a second wave of NIMH genetics initiative bipolar pedigrees: chromosomes 2, 11, 13, 14, and X

Abstract

As part of the on-going NIMH Genetics Initiative on Bipolar Disorder, we have ascertained 153 multiplex bipolar pedigrees and genotyped them in two waves. We report here the genome scan results for chromosomes 2, 11, 13, 14, and X in the second wave of 56 families. A total of 354 individuals were genotyped and included in the current analyses, including 5 with schizoaffective/bipolar (SA/BP), 139 with bipolar I disorder (BPI), 41 with bipolar II disorder (BPII), and 43 with recurrent unipolar depression (RUP). Linkage analyses were carried out with multi-point parametric and non-parametric affected relative pair methods using three different definitions of the affected phenotype: (model 1) SA/BP and BPI; (model 2) SA/BP, BPI, and BPII; and (model 3) SA/BP, BPI, BPII, and RUP. The best findings were on 11p15.5 (NPL = 2.96, P = 0.002) and Xp11.3 (NPL = 2.19, P = 0.01). These findings did not reach conventional criteria for significance, but they were located near regions that have been identified in previous genetic studies of bipolar disorder. The relatively modest but consistent findings across studies may suggest that these loci harbor susceptibility genes of modest effect in a subset of families. Large samples such as that being collected by the NIMH Initiative will be necessary to examine the heterogeneity and identify these susceptibility genes.

Candidate genes, pathways and mechanisms for alcoholism: an expanded convergent functional genomics approach

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The genetics of schizophrenia and bipolar disorder: dissecting psychosis

“…There is cross-species conservation of the precursor portion of proBDNF which is consistent with potential functional importance and it is possible that the common Val66Met polymorphism could itself have a functionally relevant effect by modifying the processing and trafficking of BDNF. 120 There have been three positive reports using family based association studies of Caucasian bipolar disorder samples of European-American origin and the Val66Met SNP: two are in (wave 3) 17q25, 6q16, 2p13, 3q23, 8q24 Dick et al, 174 Willour et al, 175 Zandi et al 176 56 NIMH pedigrees (wave 2) 11p15, Xp11, 4q35, 4q32, 20p12, 16p13…”

Genome scan of the fifty‐six bipolar pedigrees from the NIMH genetics initiative replication sample: Chromosomes 4, 7, 9, 18, 19, 20, and 21

“…Companion papers report the genome scan results for this replication pedigree set on chromosomes 2, 3, 5, 11, 13, 14, 15, 16, 17, 22, and X [Dick et al, 2002;Zandi et al, 2003]. Our site has recently genotyped these replication pedigrees for 107 microsatellite markers from chromosomes 4,7,9,18,19,20, and 21, and we now report nonparametric and parametric linkage results for these seven chromosomes.…”