title: Genetic association and sequencing of the insulin-like growth factor 1 gene in bipolar affective disorder.
abstract: Insulin-like growth factor 1 (IGF1) has been shown to have an important role in brain development and function. Studies of IGF1 administration in rodents have shown that it has an anxiolytic and antidepressant effect. A genome-wide association study (GWAS) of the first University College London (UCL) cohort of 506 bipolar affective disorder subjects and 510 controls was carried out. The exons and flanking regions of IGF1 were resequenced, any new polymorphisms found were genotyped in an enlarged UCL sample of 937 cases and 941 controls. GWAS data gave good evidence of allelic and haplotypic association between multiple IGF1 SNP's and bipolar disorder (BD). New polymorphisms were found by resequencing IGF1 region. Data from GWAS and the new markers showed that twelve out of 43 SNPs showed association with BD with the four most significant SNPs having values of 3.7 × 10(-5) , 8.4 × 10(-4) , 2.6 × 10(-4) , and 2.5 × 10(-4) . A 5' promoter microsatellite polymorphism previously correlated with plasma lipoprotein concentration was also associated with BD (P = 0.013). Haplotypic association confirmed association with BD with significance values similar to the single marker SNP values. The marker rs12426318 has also been found to be associated with BD in a second sample. A test of gene wide significance with permutation testing for all markers genotyped at IGF1 was also significant. These data implicate IGF1 as a candidate gene to cause genetic susceptibility to BD.
authors.affiliation: Molecular Psychiatry Laboratory, Department of Mental Health Sciences, Windeyer Institute of Medical Sciences, University College London, 46 Cleveland Street, London, UK.
authors.forename: Ana C Parente
authors.initials: AC
authors.lastname: Pereira
authors.forename: Andrew
authors.initials: A
authors.lastname: McQuillin
authors.forename: Vinay
authors.initials: V
authors.lastname: Puri
authors.forename: Adebayo
authors.initials: A
authors.lastname: Anjorin
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bass
authors.forename: Radhika
authors.initials: R
authors.lastname: Kandaswamy
authors.forename: Jacob
authors.initials: J
authors.lastname: Lawrence
authors.forename: David
authors.initials: D
authors.lastname: Curtis
authors.forename: Pamela
authors.initials: P
authors.lastname: Sklar
authors.forename: Shaun M
authors.initials: SM
authors.lastname: Purcell
authors.forename: Hugh M D
authors.initials: HM
authors.lastname: Gurling
mesh_terms: D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping / Q000706:statistics & numerical data; D015331:Cohort Studies; D005091:Exons; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008131:London; D018895:Microsatellite Repeats; D020641:Polymorphism, Single Nucleotide
chemical_list: D005819:Genetic Markers; D007334:Insulin-Like Growth Factor I