Hair Cortisol in Twins: Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes
Authors: Rietschel Liz , Streit Fabian , Zhu Gu , McAloney Kerrie , Frank Josef , Couvy-Duchesne Baptiste , Witt Stephanie H. , Binz Tina M. ,   CORtisolNETwork (CORNET) Consortium, Bolton Jennifer L. , Hayward Caroline , Direk Nese , Anderson Anna , Huffman Jennifer , Wilson James F. , Campbell Harry , Rudan Igor , Wright Alan , Hastie Nicholas , Wild Sarah H. , Velders Fleur P. , Hofman Albert , Uitterlinden Andre G. , Lahti Jari , Räikkönen Katri , Kajantie Eero , Widen Elisabeth , Palotie Aarno , Eriksson Johan G. , Kaakinen Marika , Järvelin Marjo-Riitta , Timpson Nicholas J. , Davey Smith George , Ring Susan M. , Evans David M. , St Pourcain Beate , Tanaka Toshiko , Milaneschi Yuri , Bandinelli Stefania , Ferrucci Luigi , van der Harst Pim , Rosmalen Judith GM , Bakker Stephen JL , Verweij Niek , Dullaart Robin PF , Mahajan Anubha , Lindgren Cecilia M. , Morris Andrew , Lind Lars , Ingelsson Erik , Anderson Laura N. , Pennell Craig E. , Lye Stephen J. , Matthews Stephen G. , Eriksson Joel , Mellstrom Dan , Ohlsson Claes , Price Jackie F. , Strachan Mark WJ , Reynolds Rebecca M. , Tiemeier Henning ,   Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (PGC), Ripke Stephan , Mattheisen Manuel , Abdellaoui Abdel , Adams Mark J. , Agerbo Esben , Air Tracy M. , Andlauer Till FM , Bacanu Silviu-Alin , Bækvad-Hansen Marie , Beekman Aartjan TF , Bennett David A. , Berger Klaus , Bigdeli Tim B. , Bybjerg-Grauholm Jonas , Byrne Enda M. , Cai Na , Castelao Enrique , Clarke Toni-Kim , Coleman Jonathan RI , Consortium Converge , Craddock Nick , Dannlowski Udo , Davies Gareth , Davies Gail , de Geus Eco. J. C. , De Jager Philip , Deary Ian J. , Degenhardt Franziska , Dunn Erin C. , Ehli Erik A. , Eley Thalia C. , Escott-Price Valentina , Esko Tõnu , Finucane Hilary K. , Gill Michael , Gordon Scott D. , Grove Jakob , Hall Lynsey S. , Hansen Thomas F. , Søholm Hansen Christine , Hansen Thomas F. , Heath Andrew C. , Henders Anjali K. , Herms Stefan , Hoffmann Per , Homuth Georg , Horn Carsten , Hottenga Jouke- Jan , Hougaard David , Huang Hailiang , Ising Marcus , Jansen Rick , Jorgenson Eric , Kloiber Stefan , Knowles James A , Kretzschmar Warren W. , Krogh Jesper , Kutalik Zoltán , Lang Maren , Lewis Glyn , Li Yihan , MacIntyre Donald J. , Madden Pamela AF , Marchine Jonathan , Mbarek Hamdi , McGuffin Peter , Mehta Divya , Metspalu Andres , Middeldorp Christel M. , Mihailov Evelin , Milani Lili , Montgomery Grant W. , Mostafavi Sara , Mullins Niamh , Nauck Matthias , Ng Bernard , Nordentoft Merete , Nyholt Dale R. , O’Donovan Michael C. , O’Reilly Paul F. , Oskarsson Hogni , Owen Michael J. , Paciga Sara A. , Pedersen Carsten Bøcker , Pedersen Marianne Giørtz , Pedersen Nancy L. , Pergadia Michele L. , Peterson Roseann E. , Pettersson Erik , Peyrot Wouter J. , Porteous David J. , Posthuma Danielle , Potash James B. , Quiroz Jorge A. , Rice John P. , Riley Brien P. , Rivera Margarita , Ruderfer Douglas M. , Saeed Mirza Saira , Schoevers Robert , Shen Ling , Shi Jianxin , Sigurdsson Engilbert , Sinnamon Grant CB , Smit Johannes H. , Smith Daniel J. , Smoller Jordan W. , Stephansson Hreinn , Steinberg Stacy , Strohmaier Jana , Tansey Katherine E. , Teumer Alexander , Thompson Wesley , Thomson Pippa A. , Thorgeirsson Thorgeir E. , Treutlein Jens , Trzaskowski Maciej , Umbricht Daniel , van der Auwera Sandra , van Grootheest Gerard , van Hemert Albert M. , Viktorin Alexander , Völzke Henry , Wang Yunpeng , Webb Bradley T. , Weissman Myrna M. , Wellmann Jürgen , Willemsen Gonneke , Xi Hualin S. , Baune Bernhard T. , Blackwood Douglas H. R. , Boomsma Dorret I. , Børglum Anders D. , Buttenschøn Henriette N. , Cichon Sven , Domenici Enrico , Flint Jonathan , Grabe Hans J. , Hamilton Steven P. , Kendler Kenneth S. , Li Qingqin S. , Lucae Susanne , Magnusson Patrik K. , McIntosh Andrew M. , Mors Ole , Bo Mortensen Preben , Müller-Myhsok Bertram , Penninx Brenda WJH , Perlis Roy H. , Preisig Martin , Schaefer Catherine , Smoller Jordan W. , Stephansson Kari , Tiemeier Henning , Uher Rudolf , Werge Thomas , Winslow Ashley R. , Breen Gerome , Levinson Douglas F. , Lewis Cathryn M. , Wray Naomi R. , Sullivan Patrick F. , McGrath John , Hickie Ian B. , Hansell Narelle K. , Wright Margaret J. , Gillespie Nathan A. , Forstner Andreas J. , Schulze Thomas G , Wüst Stefan , Nöthen Markus M. , Baumgartner Markus R. , Walker Brian R. , Crawford Andrew A. , Colodro-Conde Lucía , Medland Sarah E. , Martin Nicholas G. , Rietschel Marcella 
Published: November 2017

Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.