title: Evidence for associations between MDGA2 polymorphisms and harm avoidance: replication and extension of a genome-wide association finding.
abstract: In 2008, van den Oord et al. identified in a genome-wide association study the MAM domain containing glycosylphosphatidylinositol anchor 2 gene (MDGA2 or MAMDC1) as a new candidate for neuroticism. In addition to the replication attempt of this association, we further investigated the role of MDGA2 with respect to harm avoidance (HA), a personality trait highly related to neuroticism. In a sample of mentally healthy volunteers (n=541) and depressed patients (n=199), neuroticism and HA were assessed with Eysenck's Revised Personality Questionnaire and Cloninger's Tridimensional Personality Questionnaire. Genotypic information (Illumina Bead Chip HumanHap300) of 100 single nucleotide polymorphisms (SNPs) located in the MDGA2 gene (±5 kb) was available, and additional four SNPs for replication were imputed. We were able to replicate the association between MDGA2 and neuroticism for the strongest SNPs of the genome-wide association study. It could further be shown that volunteers homozygous for the T-allele of SNP rs2416054 showed higher scores in the HA4 subscale 'Fatigability and asthenia' (Pnominal=0.0006), remaining significant after correction for multiple testing (Pwy-corrected=0.045). The same SNP also showed an association with HA4 in the patients' sample (Pnominal=0.03). Our finding provides further support for a link between variants in the MDGA2 gene and specific neuroticism-related phenotypes.
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstrasse, Munich, Germany. angela.heck@unibas.ch
authors.forename: Angela
authors.initials: A
authors.lastname: Heck
authors.forename: Hildegard
authors.initials: H
authors.lastname: Pfister
authors.forename: Darina
authors.initials: D
authors.lastname: Czamara
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
authors.forename: Benno
authors.initials: B
authors.lastname: Pütz
authors.forename: Susanne
authors.initials: S
authors.lastname: Lucae
authors.forename: Johannes
authors.initials: J
authors.lastname: Hennings
authors.forename: Marcus
authors.initials: M
authors.lastname: Ising
mesh_terms: D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D056726:Genetic Association Studies; D055106:Genome-Wide Association Study; D040261:Harm Reduction; D006801:Humans; D008297:Male; D008875:Middle Aged; D019006:Neural Cell Adhesion Molecules / Q000235:genetics*; D010556:Personality Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D011795:Surveys and Questionnaires
chemical_list: D058851:GPI-Linked Proteins; C544522:MDGA2 protein, human; D019006:Neural Cell Adhesion Molecules