The molecular genetic architecture of self-employment

TY - JOUR

T1 - The molecular genetic architecture of self-employment

AU - van der Loos, Matthijs J H M

AU - Rietveld, Cornelius A

AU - Eklund, Niina

AU - Koellinger, Philipp D

AU - Rivadeneira, Fernando

AU - Abecasis, Gonçalo R

AU - Ankra-Badu, Georgina A

AU - Baumeister, Sebastian E

AU - Benjamin, Daniel J

AU - Biffar, Reiner

AU - Blankenberg, Stefan

AU - Boomsma, Dorret I

AU - Cesarini, David

AU - Cucca, Francesco

AU - de Geus, Eco J C

AU - Dedoussis, George

AU - Deloukas, Panos

AU - Dimitriou, Maria

AU - Eiriksdottir, Guðny

AU - Eriksson, Johan

AU - Gieger, Christian

AU - Gudnason, Vilmundur

AU - Höhne, Birgit

AU - Holle, Rolf

AU - Hottenga, Jouke-Jan

AU - Isaacs, Aaron

AU - Järvelin, Marjo-Riitta

AU - Johannesson, Magnus

AU - Kaakinen, Marika

AU - Kähönen, Mika

AU - Kanoni, Stavroula

AU - Laaksonen, Maarit A

AU - Lahti, Jari

AU - Launer, Lenore J

AU - Lehtimäki, Terho

AU - Loitfelder, Marisa

AU - Magnusson, Patrik K E

AU - Naitza, Silvia

AU - Oostra, Ben A

AU - Perola, Markus

AU - Petrovic, Katja

AU - Quaye, Lydia

AU - Raitakari, Olli

AU - Ripatti, Samuli

AU - Scheet, Paul

AU - Schlessinger, David

AU - Schmidt, Carsten O

AU - Schmidt, Helena

AU - Schmidt, Reinhold

AU - Senft, Andrea

AU - Smith, Albert V

AU - Spector, Timothy D

AU - Surakka, Ida

AU - Svento, Rauli

AU - Terracciano, Antonio

AU - Tikkanen, Emmi

AU - van Duijn, Cornelia M

AU - Viikari, Jorma

AU - Völzke, Henry

AU - Wichmann, H-Erich

AU - Wild, Philipp S

AU - Willems, Sara M

AU - Willemsen, Gonneke

AU - van Rooij, Frank J A

AU - Groenen, Patrick J F

AU - Uitterlinden, André G

AU - Hofman, Albert

AU - Thurik, A Roy

PY - 2013

Y1 - 2013

N2 - Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable-entrepreneurship-that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σ(g)(2)/σ(P)(2) = 25%, h(2) = 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with p<10(-5) were tested in a replication sample (n = 3,271), but none replicated. Furthermore, a gene-based test shows that none of the genes that were previously suggested in the literature to influence entrepreneurship reveal significant associations. Finally, SNP-based genetic scores that use results from the meta-analysis capture less than 0.2% of the variance in self-employment in an independent sample (p≥0.039). Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases.

AB - Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable-entrepreneurship-that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σ(g)(2)/σ(P)(2) = 25%, h(2) = 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with p<10(-5) were tested in a replication sample (n = 3,271), but none replicated. Furthermore, a gene-based test shows that none of the genes that were previously suggested in the literature to influence entrepreneurship reveal significant associations. Finally, SNP-based genetic scores that use results from the meta-analysis capture less than 0.2% of the variance in self-employment in an independent sample (p≥0.039). Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases.

KW - Employment

KW - Female

KW - Gene-Environment Interaction

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Intelligence

KW - Male

KW - Models, Theoretical

KW - Multifactorial Inheritance

KW - Personality

KW - Polymorphism, Single Nucleotide

KW - Registries

KW - Twins, Dizygotic

KW - Twins, Monozygotic

U2 - 10.1371/journal.pone.0060542

DO - 10.1371/journal.pone.0060542

M3 - SCORING: Journal article

C2 - 23593239

VL - 8

SP - e60542

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 4

ER -