Meta-analysis of genome-wide association studies for personality

Marleen H.M. de Moor (1) , Antonio Terracciano (1) , Robert Krueger (1) , Eco de Geus (1) , Toshiko Tanaka (1) , Brenda W.J.H. Penninx (1) , Tonu Esko (1) , Pamela Madden (1) , Jaime Derringer (1) , Najaf Amin (1) , G. Willemsen (1) , Jouke-Jan Hottenga (1) , Marijn Distel (1) , Manuela Uda (1) , Serena Sanna (1) , Philip Spinhoven (1) , Catharina Hartman (1) , Patrick Sullivan (1) , Anu Realo (1) , Jüri Allik (1) , Andrew Heath (1) , Michele Pergadia (1) , Arpana Agrawal (1) , Peng Lin (1) , Richard Grucza (1) , Elisabeth Widen (1) , Diana Cousminer (1) , Johan Eriksson (1) , Aarno Palotie (1) , Leena Peltonen (1) , Michelle Luciano (1) , Albert Tenesa (1) , Gail Davies (1) , Lorna Lopez (1) , Narelle Hansell (1) , Sarah Medland (1) , Luigi Ferrucci (1) , David Schlessinger (1) , Grant W. Montgomery (1) , Margaret Wright (1) , Yurii Aulchenko (1) , Cecile Janssens (1) , Ben A. Oostra (1) , Andres Metspalu (1) , Goncalo Abecasis (1) , Ian Deary (1) , Katri Räikkönen (1) , Laura J. Bierut (1) , Nick Martin (1) , Dorret Boomsma (1) , Cornelia van Duijn (1) , Paul Costa (1) , Teresa Nutile (1) , Marina Ciullo (1) , Dan Rujescu (1) , Ina Giegling (1) , Bettina Konte (1)

1 Medstar Research Institute

Personality can be thought of as a set of characteristics that influence people's thoughts, feelings, and behaviour across a variety of settings. Variation in personality is predictive of many outcomes in life, including mental health. Here we report on a meta-analysis of genome-wide association (GWA) data for personality in ten discovery samples (17 375 adults) and five in-silico replication samples (3 294 adults). All participants were of European ancestry. Personality scores for Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness were based on the NEO Five-Factor Inventory. Genotype data were available of ~2.4M Single Nucleotide Polymorphisms (SNPs; directly typed and imputed using HAPMAP data). In the discovery samples, classical association analyses were performed under an additive model followed by meta-analysis using the weighted inverse variance method. Results showed genome-wide significance for Openness to Experience near the RASA1 gene on 5q14.3 (rs1477268 and rs2032794, P = 2.8 x 10-8 and 3.1 x 10-8) and for Conscientiousness in the brain-expressed KATNAL2 gene on 18q21.1 (rs2576037, P = 4.9 x 10-8). We further conducted a gene-based test that confirmed the association of KATNAL2 to Conscientiousness. In-silico replication did not, however, show significant associations of the top SNPs with Openness and Conscientiousness, although the direction of effect of the KATNAL2 SNP on Conscientiousness was consistent in all replication samples. Larger scale GWA studies and alternative approaches are required for confirmation of KATNAL2 as a novel gene affecting Conscientiousness.

Mots clés: Personality; Five-Factor Model; Genome-wide association; Meta-analysis; Genetic variants

Marleen H.M. de Moor, Antonio Terracciano, Robert Krueger, Eco de Geus, Toshiko Tanaka, et al.. Meta-analysis of genome-wide association studies for personality. Molecular Psychiatry, 2010, ⟨10.1038/mp.2010.128⟩. ⟨hal-00601880⟩