TY - JOUR
T1 - Refining genome-wide linkage intervals using a meta-analysis of genome-wide association studies identifies loci influencing personality dimensions
AU - Amin, Najaf
AU - Hottenga, Jouke Jan
AU - Hansell, Narelle K.
AU - Janssens, A. Cecile J.W.
AU - De Moor, Marleen H.M.
AU - Madden, Pamela A.F.
AU - Zorkoltseva, Irina V.
AU - Penninx, Brenda W.
AU - Terracciano, Antonio
AU - Uda, Manuela
AU - Tanaka, Toshiko
AU - Esko, Tonu
AU - Realo, Anu
AU - Ferrucci, Luigi
AU - Luciano, Michelle
AU - Davies, Gail
AU - Metspalu, Andres
AU - Abecasis, Goncalo R.
AU - Deary, Ian J.
AU - Raikkonen, Katri
AU - Bierut, Laura J.
AU - Costa, Paul T.
AU - Saviouk, Viatcheslav
AU - Zhu, Gu
AU - Kirichenko, Anatoly V.
AU - Isaacs, Aaron
AU - Aulchenko, Yurii S.
AU - Willemsen, Gonneke
AU - Heath, Andrew C.
AU - Pergadia, Michele L.
AU - Medland, Sarah E.
AU - Axenovich, Tatiana I.
AU - De Geus, Eco
AU - Montgomery, Grant W.
AU - Wright, Margaret J.
AU - Oostra, Ben A.
AU - Martin, Nicholas G.
AU - Boomsma, Dorret I.
AU - Van Duijn, Cornelia M.
N1 - Funding Information:
ERF: The genotyping for the ERF study was supported by EUROSPAN (European Special Populations Research Network) and the European Commission FP6 STRP Grant (018947; LSHG-CT-2006-01947). The ERF study was further supported by grants from the Netherlands Organization for Scientific Research, Erasmus MC, the Center for Medical Systems Biology (CMSB) and the Netherlands Brain Foundation (HersenStichting Nederland).
Funding Information:
QIMR: We thank Marlene Grace and Ann Eldridge for sample collection; Anjali Henders, Megan Campbell, Lisa Bowdler, Steven Crooks and staff of the Molecular Epidemiology Laboratory for sample processing and preparation; Harry Beeby, David Smyth and Daniel Park for IT support. We acknowledge support from the Australian Research Council (A7960034, A79906588, A79801419, DP0212016 and DP0343921), Beyond Blue and the Borderline Personality Disorder Research Foundation. Genotyping was funded by the National Health and Medical Research Council (Medical Bioinformatics Genomics Proteomics Program, 389891). Further, we gratefully acknowledge Drs Dale R Nyholt and especially Scott Gordon for their substantial efforts involving the QC and preparation of the QIMR and NAG/IRPG GWA data sets from which SNPs were selected. Dr Nyholt also contributed 8% of the NAG/IRPG GWA cohort (NHMRC IDs 339462, 442981, 389938 and 496739). In addition, we thank him for helpful discussions regarding methodology. GWAS cohorts: We also acknowledge the individual contributions of the cohorts included in the meta-analysis of genome-wide association scans. Paul T Costa Jr receives royalties from the NEO-FFI. Laura J Bierut is an inventor on the patent ‘Markers for Addiction’ (US 20070258898) covering the use of certain SNPs in determining the diagnosis, prognosis and treatment of addiction. Dr Bierut served as a consultant for Pfizer Inc. in 2008.
Funding Information:
We are grateful to all patients and their relatives, general practitioners and neurologists for their contributions, and to P Veraart for her help in genealogy, Jeannette Vergeer for the supervision of the laboratory work and P Snijders for his help in data collection. NTR: We acknowledge financial support from the Netherlands Organization for Scientific Research (NWO): Grants 575-25-006, 480-04-004, 904-61-090; 904-61-193, 400-05-717 and Spinozapremie SPI 56-464-14192. MHMdeM is financially supported by ZonMW (Addiction) Grant number 311-60008. We further acknowledge financial support from the Center for Medical Systems Biology (NWO Genomics), Neuroscience Campus Amsterdam; EU/QLRT-2001-01254; NIMH R01 MH059160; Geestkracht program of ZonMW (10-000-1002); and matching funds from universities and mental health care institutes involved in NESDA. Genotyping was funded by the Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health, and analysis was supported by grants from GAIN and the NIMH (MH081802). Genotype data were obtained from dbGaP (http://www.ncbi.nlm.nih.gov/dbgap, accession number phs000020.v1.p1).
PY - 2013/8
Y1 - 2013/8
N2 - Personality traits are complex phenotypes related to psychosomatic health. Individually, various gene finding methods have not achieved much success in finding genetic variants associated with personality traits. We performed a meta-analysis of four genome-wide linkage scans (N=6149 subjects) of five basic personality traits assessed with the NEO Five-Factor Inventory. We compared the significant regions from the meta-analysis of linkage scans with the results of a meta-analysis of genome-wide association studies (GWAS) (N∼17 000). We found significant evidence of linkage of neuroticism to chromosome 3p14 (rs1490265, LOD=4.67) and to chromosome 19q13 (rs628604, LOD=3.55); of extraversion to 14q32 (ATGG002, LOD=3.3); and of agreeableness to 3p25 (rs709160, LOD=3.67) and to two adjacent regions on chromosome 15, including 15q13 (rs970408, LOD=4.07) and 15q14 (rs1055356, LOD=3.52) in the individual scans. In the meta-analysis, we found strong evidence of linkage of extraversion to 4q34, 9q34, 10q24 and 11q22, openness to 2p25, 3q26, 9p21, 11q24, 15q26 and 19q13 and agreeableness to 4q34 and 19p13. Significant evidence of association in the GWAS was detected between openness and rs677035 at 11q24 (P-value=2.6 × 10 -06, KCNJ1). The findings of our linkage meta-analysis and those of the GWAS suggest that 11q24 is a susceptible locus for openness, with KCNJ1 as the possible candidate gene.
AB - Personality traits are complex phenotypes related to psychosomatic health. Individually, various gene finding methods have not achieved much success in finding genetic variants associated with personality traits. We performed a meta-analysis of four genome-wide linkage scans (N=6149 subjects) of five basic personality traits assessed with the NEO Five-Factor Inventory. We compared the significant regions from the meta-analysis of linkage scans with the results of a meta-analysis of genome-wide association studies (GWAS) (N∼17 000). We found significant evidence of linkage of neuroticism to chromosome 3p14 (rs1490265, LOD=4.67) and to chromosome 19q13 (rs628604, LOD=3.55); of extraversion to 14q32 (ATGG002, LOD=3.3); and of agreeableness to 3p25 (rs709160, LOD=3.67) and to two adjacent regions on chromosome 15, including 15q13 (rs970408, LOD=4.07) and 15q14 (rs1055356, LOD=3.52) in the individual scans. In the meta-analysis, we found strong evidence of linkage of extraversion to 4q34, 9q34, 10q24 and 11q22, openness to 2p25, 3q26, 9p21, 11q24, 15q26 and 19q13 and agreeableness to 4q34 and 19p13. Significant evidence of association in the GWAS was detected between openness and rs677035 at 11q24 (P-value=2.6 × 10 -06, KCNJ1). The findings of our linkage meta-analysis and those of the GWAS suggest that 11q24 is a susceptible locus for openness, with KCNJ1 as the possible candidate gene.
KW - GSMA
KW - KCNJ1
KW - Linkage
KW - NEO
KW - Personality
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U2 - 10.1038/ejhg.2012.263
DO - 10.1038/ejhg.2012.263
M3 - Article
C2 - 23211697
AN - SCOPUS:84880924707
SN - 1018-4813
VL - 21
SP - 876
EP - 882
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 8
ER -