ABSTRACT
We performed a genome-wide association scan in 1461 patients with bipolar (BP) 1 disorder, 2008 controls drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder and the University College London sample collections with successful genotyping for 372,193 single nucleotide polymorphisms (SNPs). Our strongest single SNP results are found in myosin5B (MYO5B; P=1.66 x 10(-7)) and tetraspanin-8 (TSPAN8; P=6.11 x 10(-7)). Haplotype analysis further supported single SNP results highlighting MYO5B, TSPAN8 and the epidermal growth factor receptor (MYO5B; P=2.04 x 10(-8), TSPAN8; P=7.57 x 10(-7) and EGFR; P=8.36 x 10(-8)). For replication, we genotyped 304 SNPs in family-based NIMH samples (n=409 trios) and University of Edinburgh case-control samples (n=365 cases, 351 controls) that did not provide independent replication after correction for multiple testing. A comparison of our strongest associations with the genome-wide scan of 1868 patients with BP disorder and 2938 controls who completed the scan as part of the Wellcome Trust Case-Control Consortium indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene. Given the heritability of BP disorder, the lack of agreement between studies emphasizes that susceptibility alleles are likely to be modest in effect size and require even larger samples for detection.
Subject(s)
Antigens, Neoplasm/genetics , Bipolar Disorder/genetics , ErbB Receptors/genetics , Genome, Human , Membrane Glycoproteins/genetics , Myosin Heavy Chains/genetics , Myosin Type V/genetics , Polymorphism, Single Nucleotide , Chromosome Mapping , DNA/genetics , DNA/isolation & purification , Gene Frequency , Genetic Markers , Genotype , Humans , Medical History Taking , Patient Selection , Reference Values , TetraspaninsABSTRACT
Equipment is described for measuring the pull exerted by mice to escape tail restraint and enter a black box. Alcohol, at doses exceeding about 2.5 g/kg, intraperitoneally, significantly decreased "muscle pull", measured 5-60 min after administration. Fifty per cent depression of muscle pull was obtained with doses of about 3.04, 3.18 and 3.55 g/kg of alcohol, 15, 30 and 60 min after alcohol administration, respectively. Depression of muscle pull correlated with alcohol concentrations in the blood plasma. The data show that muscle pull was decreased in only a few animals with plasma alcohol concentrations of less than about 250 mg%, but was significantly depressed in animals with plasma alcohol concentrations of 350 mg% or more. Although differing from it in some respects, the method described is similar to the tilting-plane method which has been used in studies dealing with the effect of alcohol in rats and mice.
