van den Berg Stéphanie M, de Moor Marleen H M, Verweij Karin J H, Krueger Robert F, Luciano Michelle, Arias Vasquez Alejandro, Matteson Lindsay K, Derringer Jaime, Esko Tõnu, Amin Najaf, Gordon Scott D, Hansell Narelle K, Hart Amy B, Seppälä Ilkka, Huffman Jennifer E, Konte Bettina, Lahti Jari, Lee Minyoung, Miller Mike, Nutile Teresa, Tanaka Toshiko, Teumer Alexander, Viktorin Alexander, Wedenoja Juho, Abdellaoui Abdel, Abecasis Goncalo R, Adkins Daniel E, Agrawal Arpana, Allik Jüri, Appel Katja, Bigdeli Timothy B, Busonero Fabio, Campbell Harry, Costa Paul T, Smith George Davey, Davies Gail, de Wit Harriet, Ding Jun, Engelhardt Barbara E, Eriksson Johan G, Fedko Iryna O, Ferrucci Luigi, Franke Barbara, Giegling Ina, Grucza Richard, Hartmann Annette M, Heath Andrew C, Heinonen Kati, Henders Anjali K, Homuth Georg, Hottenga Jouke-Jan, Iacono William G, Janzing Joost, Jokela Markus, Karlsson Robert, Kemp John P, Kirkpatrick Matthew G, Latvala Antti, Lehtimäki Terho, Liewald David C, Madden Pamela A F, Magri Chiara, Magnusson Patrik K E, Marten Jonathan, Maschio Andrea, Mbarek Hamdi, Medland Sarah E, Mihailov Evelin, Milaneschi Yuri, Montgomery Grant W, Nauck Matthias, Nivard Michel G, Ouwens Klaasjan G, Palotie Aarno, Pettersson Erik, Polasek Ozren, Qian Yong, Pulkki-Råback Laura, Raitakari Olli T, Realo Anu, Rose Richard J, Ruggiero Daniela, Schmidt Carsten O, Slutske Wendy S, Sorice Rossella, Starr John M, St Pourcain Beate, Sutin Angelina R, Timpson Nicholas J, Trochet Holly, Vermeulen Sita, Vuoksimaa Eero, Widen Elisabeth, Wouda Jasper, Wright Margaret J, Zgaga Lina, Porteous David, Minelli Alessandra, Palmer Abraham A, Rujescu Dan, Ciullo Marina, Hayward Caroline, Rudan Igor, Metspalu Andres, Kaprio Jaakko, Deary Ian J, Räikkönen Katri, Wilson James F, Keltikangas-Järvinen Liisa, Bierut Laura J, Hettema John M, Grabe Hans J, Penninx Brenda W J H, van Duijn Cornelia M, Evans David M, Schlessinger David, Pedersen Nancy L, Terracciano Antonio, McGue Matt, Martin Nicholas G, Boomsma Dorret I
Department of Research Methodology, Measurement and Data-Analysis (OMD), Faculty of Behavioural, Management, and Social Sciences, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands.
Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
Behav Genet. 2016 Mar;46(2):170-82. doi: 10.1007/s10519-015-9735-5. Epub 2015 Sep 11.
Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.
外向性是一种相对稳定且可遗传的人格特质,与众多心理社会、生活方式和健康结果相关。尽管其具有较高的遗传性,但在以往的全基因组关联(GWA)研究中尚未检测到相关基因变异,这可能是由于这些研究的样本量相对较小。在此,我们报告了一项对29个队列中63,030名受试者的外向性GWA研究的大型荟萃分析。来自多个人格量表的外向性项目数据在量表和队列之间进行了统一。在单核苷酸多态性(SNP)水平上未发现全基因组显著关联,但在一个长链非编码RNA位点(LOC101928162)的基因水平上有一个显著结果。在两个大型队列中的全基因组复杂性状分析表明,常见SNP解释的加性方差与零无显著差异,但使用连锁信息加权的多基因风险评分在一个独立队列中显著预测了外向性得分。这些结果表明,外向性是一种高度多基因的人格特质,其结构可能与其他复杂人类特质(包括其他人格特质)不同。未来的研究需要进一步确定哪些基因变异通过何种基因作用模式构成了外向性的遗传性。