Hair Cortisol in Twins: Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes
Rietschel L., Streit F., Zhu G., McAloney K., Frank J., Couvy-Duchesne B., Witt SH., Binz TM., Bolton JL., Hayward C., Direk N., Anderson A., Huffman J., Wilson JF., Campbell H., Rudan I., Wright A., Hastie N., Wild SH., Velders FP., Hofman A., Uitterlinden AG., Lahti J., Räikkönen K., Kajantie E., Widen E., Palotie A., Eriksson JG., Kaakinen M., Järvelin M-R., Timpson NJ., Davey Smith G., Ring SM., Evans DM., St Pourcain B., Tanaka T., Milaneschi Y., Bandinelli S., Ferrucci L., van der Harst P., Rosmalen JGM., Bakker SJL., Verweij N., Dullaart RPF., Mahajan A., Lindgren CM., Morris A., Lind L., Ingelsson E., Anderson LN., Pennell CE., Lye SJ., Matthews SG., Eriksson J., Mellstrom D., Ohlsson C., Price JF., Strachan MWJ., Reynolds RM., Tiemeier H., Ripke S., Mattheisen M., Abdellaoui A., Adams MJ., Agerbo E., Air TM., Andlauer TFM., Bacanu S-A., Bækvad-Hansen M., Beekman ATF., Bennett DA., Berger K., Bigdeli TB., Bybjerg-Grauholm J., Byrne EM., Cai N., Castelao E., Clarke T-K., Coleman JRI., Consortium C., Craddock N., Dannlowski U., Davies G., Davies G., de Geus EJC., De Jager P., Deary IJ., Degenhardt F., Dunn EC., Ehli EA., Eley TC., Escott-Price V., Esko T., Finucane HK., Gill M., Gordon SD., Grove J., Hall LS., Hansen TF., Søholm Hansen C., Hansen TF., Heath AC., Henders AK., Herms S., Hoffmann P., Homuth G., Horn C., Hottenga J-J., Hougaard D., Huang H., Ising M., Jansen R., Jorgenson E., Kloiber S., Knowles JA., Kretzschmar WW., Krogh J., Kutalik Z., Lang M., Lewis G., Li Y., MacIntyre DJ., Madden PAF., Marchine J., Mbarek H., McGuffin P., Mehta D., Metspalu A., Middeldorp CM., Mihailov E., Milani L., Montgomery GW., Mostafavi S., Mullins N., Nauck M., Ng B., Nordentoft M., Nyholt DR., O’Donovan MC., O’Reilly PF., Oskarsson H., Owen MJ., Paciga SA., Pedersen CB., Pedersen MG., Pedersen NL., Pergadia ML., Peterson RE., Pettersson E., Peyrot WJ., Porteous DJ., Posthuma D., Potash JB., Quiroz JA., Rice JP., Riley BP., Rivera M., Ruderfer DM., Saeed Mirza S., Schoevers R., Shen L., Shi J., Sigurdsson E., Sinnamon GCB., Smit JH., Smith DJ., Smoller JW., Stephansson H., Steinberg S., Strohmaier J., Tansey KE., Teumer A., Thompson W., Thomson PA., Thorgeirsson TE., Treutlein J., Trzaskowski M., Umbricht D., van der Auwera S., van Grootheest G., van Hemert AM., Viktorin A., Völzke H., Wang Y., Webb BT., Weissman MM., Wellmann J., Willemsen G., Xi HS., Baune BT., Blackwood DHR., Boomsma DI., Børglum AD., Buttenschøn HN., Cichon S., Domenici E., Flint J., Grabe HJ., Hamilton SP., Kendler KS., Li QS., Lucae S., Magnusson PK., McIntosh AM., Mors O., Bo Mortensen P., Müller-Myhsok B., Penninx BWJH., Perlis RH., Preisig M., Schaefer C., Smoller JW., Stephansson K., Tiemeier H., Uher R., Werge T., Winslow AR., Breen G., Levinson DF., Lewis CM., Wray NR., Sullivan PF., McGrath J., Hickie IB., Hansell NK., Wright MJ., Gillespie NA., Forstner AJ., Schulze TG., Wüst S., Nöthen MM., Baumgartner MR., Walker BR., Crawford AA., Colodro-Conde L., Medland SE., Martin NG., Rietschel M.
AbstractHair 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.