Harmonization of neuroticism and extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: An application of item response theory

Stéphanie M. Van Den Berg, Marleen H M De Moor, Matt McGue, Erik Pettersson, Antonio Terracciano, Karin J H Verweij, Najaf Amin, Jaime Derringer, Tõnu Esko, Gerard Van Grootheest, Narelle K. Hansell, Jennifer Huffman, Bettina Konte, Jari Lahti, Michelle Luciano, Lindsay K. Matteson, Alexander Viktorin, Jasper Wouda, Arpana Agrawal, Jüri AllikLaura Bierut, Ulla Broms, Harry Campbell, George Davey Smith, Johan G. Eriksson, Luigi Ferrucci, Barbera Franke, Jean Paul Fox, Eco J C De Geus, Ina Giegling, Alan J. Gow, Richard Grucza, Annette M. Hartmann, Andrew C. Heath, Kauko Heikkilä, William G. Iacono, Joost Janzing, Markus Jokela, Lambertus Kiemeney, Terho Lehtimäki, Pamela A F Madden, Patrik K E Magnusson, Kate Northstone, Teresa Nutile, Klaasjan G. Ouwens, Aarno Palotie, Alison Pattie, Anu Katriina Pesonen, Ozren Polasek, Lea Pulkkinen, Laura Pulkki-Råback, Olli T. Raitakari, Anu Realo, Richard J. Rose, Daniela Ruggiero, Ilkka Seppälä, Wendy S. Slutske, David C. Smyth, Rossella Sorice, John M. Starr, Angelina R. Sutin, Toshiko Tanaka, Josine Verhagen, Sita Vermeulen, Eero Vuoksimaa, Elisabeth Widen, Gonneke Willemsen, Margaret J. Wright, Lina Zgaga, Dan Rujescu, Andres Metspalu, James F. Wilson, Marina Ciullo, Caroline Hayward, Igor Rudan, Ian J. Deary, Katri Räikkönen, Alejandro Arias Vasquez, Paul T. Costa, Liisa Keltikangas-Järvinen, Cornelia M. Van Duijn, Brenda W J H Penninx, Robert F. Krueger, David M. Evans, Jaakko Kaprio, Nancy L. Pedersen, Nicholas G. Martin, Dorret I. Boomsma

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.

Original languageEnglish (US)
Pages (from-to)295-313
Number of pages19
JournalBehavior genetics
Volume44
Issue number4
DOIs
StatePublished - Jul 2014

Bibliographical note

Funding Information:
The Finnish Twin Cohort acknowledges NIH grants DA12854 to P A F Madden; AA-12502, AA-00145, and AA-09203 to R J Rose; AA15416 to D M Dick; and Academy of Finland grants 118555, 141054, 265240, 263278, and 264146 to J Kaprio.

Funding Information:
Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative [GEI] (U01 HG004422). SAGE is one of the GWA studies funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of datasets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401) and the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392).

Funding Information:
Cilento give special thanks to the Cilento populations for their participation in the study, acknowledge Dr. Maria Enza Amendola for the test administration and thank the personnel working in the organization of the study in the villages. This work was supported by grants from the Fondazione CON IL SUD (2011-PDR-13) and the Fondazione Banco di Napoli to MC.

Funding Information:
The BLSA was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging.

Funding Information:
HBCS thanks all study participants as well as everybody involved in the Helsinki Birth Cohort Study. Helsinki Birth Cohort Study has been supported by grants from the Academy of Finland, the Finnish Diabetes Research Society, Folkhälsan Research Foundation, Novo Nordisk Foundation, Finska Läkaresällskapet, Signe and Ane Gyl-lenberg Foundation, University of Helsinki, Ministry of Education, Ahokas Foundation, Emil Aaltonen Foundation.

Funding Information:
The STR is financially supported by the Swedish Ministry for Higher Education For the various projects financial support has been provided by: TwinGene; the Swedish Research Council (M-2005-1112), GenomEUtwin (EU/QLRT-2001-01254; QLG2-CT-2002-01254), NIH DK U01-066134, The Swedish Foundation for Strategic Research (SSF), the Heart and Lung foundation no. 20070481. STOPPA; the Strategic Research Program in Epidemiology at Kar-olinska Institutet, the Swedish Research Council (grant number 2011-3060), the Swedish Asthma and Allergy Association and the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet. CATSS; support was provided by the Swedish Council for Working Life and Social Research, the Swedish Research Council, System-bolaget, the National Board of Forensic Medicine, the Swedish Prison and Probation Service, Bank of Sweden Tercentenary Foundation, the Söderström–Königska foundation, and the Karolinska Institutet Center of Neurodevelopmental Disorders (KIND). BIRTH; supported by the Swedish Council for Working Life and Social Research (2004-0174 and 2007-0231), the Swedish Research Council (K2006-71X-14676-04-2 and 2008-54 9 20638-01-3), the Swedish Cancer Society (4594-B01-01XAC and 4594-B04-04XAB), and the European Union-funded Network of Excellence Lifespan (FP6036894).

Funding Information:
NESDA acknowledges financial support from the Geestkracht program of the Netherlands Organisation for Health Research and Development (ZonMW, grant number 10-000-1002) and participating institutes (VU University Medical Center, GGZ inGeest, Leiden

Funding Information:
The CROATIA-Vis study was funded by grants from the Medical Research Council (UK) and Republic of Croatia Ministry of Science, Education and Sports research grants to I.R. (108-1080315-0302). We would like to acknowledge the staff of several institutions in Croatia that supported the fieldwork, including but not limited to The University of Split and Zagreb Medical Schools, the Institute for Anthropological Research in Zagreb and Croatian Institute for Public Health.

Funding Information:
ALSPAC thanks all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The UK Medical Research Council and the Wellcome Trust (Grant ref: 092731) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and DME, KN and GDS will serve as guarantors for the contents of this paper.

Funding Information:
QIMR adults We acknowledge financial support from NIH (DA12854, AA07728, AA10248, AA07580, AA11998, AA13320, AA13321, AA13326, DA019951, AA014041, AA07535, MH66206, AGO4954 and GM30250), the Australian National Health and Medical Research Council, Gemini Genomics Plc, the Borderline Personality Disorder Research Foundation, the Australian Associated Brewers, ADAMHA (AA06781 and MH40828), and the American Cancer Society (IRG-58-010-50).

Funding Information:
LBC1921 and LBC1936 phenotype collection was carried out within the Centre for Cognitive Ageing and Cognitive Epidemiology funded by a Lifelong Health and Wellbeing initiative (G0700704/ 84698). LBC1921 also acknowledge financial support from the Scottish Executive Chief Scientist Office (CZG/3/2/79) and BBSRC (15/SAG09977). LBC1936 also acknowledge financial support from Research into Ageing (Grant No. 251) and Age UK (Disconnected Mind grant).

Funding Information:
QIMR adolescents We acknowledge financial support from the Australian Research Council (A79600334, A79906588, A79801419, DP0212016, DP0343921, DP0664638, DP1093900), Beyond Blue, and the Borderline Personality Disorder Research Foundation.

Funding Information:
The CROATIA-Korcula study was funded by grants from the Medical Research Council (UK), European Commission Framework 6 project EUROSPAN (Contract No. LSHG-CT-2006-018947) and Republic of Croatia Ministry of Science, Education and Sports research grants to I.R. (108-1080315-0302). We would like to acknowledge the invaluable contributions of the recruitment team in Korcula, the administrative teams in Croatia and Edinburgh and the people of Korcula.

Funding Information:
MCTFR acknowledges support by the National Institutes of Health under award numbers R37DA005147, R01AA009367, R01AA011886, R01DA013240, and R01MH066140.

Funding Information:
The Collaborative Genetic Study of Nicotine Dependence (COG-END) project is a collaborative research group and part of the NIDA Genetics Consortium. Subject collection was supported by NIH grant P01 CA089392 (L.J. Bierut) from the National Cancer Institute. Phenotypic and genotypic data are stored in the NIDA Center for Genetic Studies (NCGS) at http://zork.wustl.edu/under NIDA Contract HHSN271200477451C (J. Tischfield and J. Rice).

Funding Information:
Acknowledgments Phenotype harmonization was financially supported by the European Network of Genomic and Genetic Epidemiology (ENGAGE).

Funding Information:
The ERF study as a part of EUROSPAN (European Special Populations Research Network) was supported by European Commission FP6 STRP grant number 018947 (LSHG-CT-2006-01947) and also received funding from the European Community’s Seventh Frame-work Programme (FP7/2007-2013)/grant agreement HEALTH-F4-2007-201413 by the European Commission under the programme ‘‘Quality of Life and Management of the Living Resources’’ of 5th Framework Programme (no. QLG2-CT-2002-01254). We are grateful to all study participants and their relatives, general practitioners and neurologists for their contributions and to P. Veraart for her help in genealogy, J. Vergeer for the supervision of the laboratory work and P. Snijders for his help in data collection.

Funding Information:
NTR acknowledges financial support from the Netherlands Organization for Scientific Research (NWO) Grants No. 575-25-006, 480-04-004, 904-61-090; 904-61-193, 400-05-717, 311-60008 and Spinozapremie SPI 56-464-14192 and the European Research Council (ERC 230374). MHMdeM is financially supported by NWO VENI Grant No. 016-115-035.

Funding Information:
Funding support for the Study of Addiction Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative [GEI] (U01 HG004422). SAGE is one of the GWA studies funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of datasets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401) and the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392).

Funding Information:
ORCADES was supported by the Chief Scientist Office of the Scottish Government, the Royal Society, the MRC Human Genetics Unit, Arthritis Research UK and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947). DNA extractions were performed at the Wellcome Trust Clinical Research Facility in Edinburgh. We would like to acknowledge the research nurses in Orkney, the administrative team in Edinburgh and the people of Orkney.

Funding Information:
The Collaborative Study on the Genetics of Alcoholism (COGA), Principal Investigators B. Porjesz, V. Hesselbrock, H. Edenberg, L. Bierut, includes ten different centers: University of Connecticut (V.Hesselbrock); Indiana University (H.J. Edenberg, J. Nurnberger Jr., T. Foroud); University of Iowa (S. Kuperman, J. Kramer); SUNY Downstate (B. Porjesz); Washington University in St. Louis (L.Bie-rut, A. Goate, J. Rice, K. Bucholz); University of California at San Diego (M. Schuckit); Rutgers University (J. Tischfield); Texas Biomedical Research Institute (L. Almasy), Howard University (R.Taylor) and Virginia Commonwealth University (D. Dick). Other COGA collaborators include: L. Bauer (University of Connecticut); D. Koller, S. O’Connor, L. Wetherill, X. Xuei (Indiana University); Grace Chan (University of Iowa); S. Kang, N. Manz, M. Rangaswamy (SUNY Downstate); J. Rohrbaugh, J-C Wang (Washington University in St. Louis); A. Brooks (Rutgers University); and F. Aliev (Virginia Commonwealth University). A. Parsian and M. Reilly are the NIAAA Staff Collaborators. This national collaborative study is supported by NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA).

Keywords

  • Consortium
  • Genome-wide association studies
  • Item-Response Theory
  • Measurement
  • Meta-analysis
  • Personality

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