The low single nucleotide polymorphism heritability of plasma and saliva cortisol levels

PSYCHONEUROENDOCRINOLOGY

卷:85

Article

Neumann, Alexander¹  Direk, Nese²  Crawford, Andrew A.^3,4  Mirza, Saira²  Adams, Hieab²  Bolton, Jennifer³  Hayward, Caroline¹⁵  Strachan, David P.⁵  Payne, Erin K.^6,7  Smith, Jennifer A.^6,8  Milaneschi, Yuri^9,10  Penninx, Brenda^9,10  Hottenga, Jouke J.¹¹  de Geus, Eco¹¹  Oldehinkel, Albertine J.¹²  van der Most, Peter J.¹³  de Rijke, Yolanda¹⁴  Walker, Brian R.³  Tiemeier, Henning^1,2 

[1] Erasmus MC Univ, Med Ctr Rotterdam, Dept Child & Adolescent Psychiat Psychol, POB 2060, NL-3000 CB Rotterdam, Netherlands

[2] Erasmus MC Univ, Med Ctr Rotterdam, Dept Epidemiol, POB 2040, NL-3000 CA Rotterdam, Netherlands

[3] Univ Edinburgh, Queens Med Res Inst, BHF Ctr Cardiovasc Sci, 47 Little France Crescent, Edinburgh EH16 4TJ, Midlothian, Scotland

[4] Univ Bristol, Sch Social & Community Med, MRC IEU, 39 Whatley Rd, Bristol BS8 2PS, Avon, England

[5] St Georges Univ London, Populat Hlth Res Inst, Cratuner Terrace, London SW17 ORE, England

[6] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, 1415 Washington Hts, Ann Arbor, MI 48109 USA

[7] Northrop Grumman Hlth Div, Life Sci Program, 7575 Colshire Dr, Mclean, VA 22102 USA

[8] Univ Michigan, Inst Social Res, Survey Res Ctr, POB 1248, Ann Arbor, MI 48106 USA

[9] Vrije Univ Amsterdam, Med Ctr GGZ Geest, Amsterdam Publ Hlth, Dept Psychiat, POB 7057, NL-1007 MB Amsterdam, Netherlands

[10] Vrije Univ Amsterdam, Med Ctr GGZ Geest, Amsterdam Neurosci, POB 7057, NL-1007 MB Amsterdam, Netherlands

[11] Vrije Univ Amsterdam, Dept Biol Psychol, Boechorststr 1, NL-1081 BT Amsterdam, Netherlands

[12] Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, POB 30-001, NL-9700 RB Groningen, Netherlands

[13] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, POB 30-001, NL-9700 RB Groningen, Netherlands

[14] Erasmus MC Univ, Med Ctr, Dept Clin Chem, POB 2040, NL-3000 CA Rotterdam, Netherlands

[15] Univ Edinburgh, Inst Genet & Mol Med, Human Genet Unit, Med Res Council, Edinburgh EH4 2XU, Midlothian, Scotland

关键词: Cortisol;    Genetics;    Heritability;    GWAS;    Single nucleotide polymorphism;   

DOI  :  10.1016/j.psyneuen.2017.08.011

来源: Elsevier

【 摘 要 】

Cortisol is an important stress hormone affected by a variety of biological and environmental factors, such as the circadian rhythm, exercise and psychological stress. Cortisol is mostly measured using blood or saliva samples. A number of genetic variants have been found to contribute to cortisol levels with these methods. While the effects of several specific single genetic variants is known, the joint genome-wide contribution to cortisol levels is unclear. Our aim was to estimate the amount of cortisol variance explained by common single nucleotide polymorphisms, i.e. the SNP heritability, using a variety of cortisol measures, cohorts and analysis approaches. We analyzed morning plasma (n = 5705) and saliva levels (n = 1717), as well as diurnal saliva levels (n = 1541), in the Rotterdam Study using genomic restricted maximum likelihood estimation. Additionally, linkage disequilibrium score regression was fitted on the results of genome-wide association studies (GWAS) performed by the CORNET consortium on morning plasma cortisol (n = 12,597) and saliva cortisol (n = 7703). No significant SNP heritability was detected for any cortisol measure, sample or analysis approach. Point estimates ranged from 0% to 9%. Morning plasma cortisol in the CORNET cohorts, the sample with the most power, had a 6% [95%CI: 0-13%] SNP heritability. The results consistently suggest a low SNP heritability of these acute and short-term measures of cortisol. The low SNP heritability may reflect the substantial environmental and, in particular, situational component of these cortisol measures. Future GWAS will require very large sample sizes. Alternatively, more long-term cortisol measures such as hair cortisol samples are needed to discover further genetic pathways regulating cortisol concentrations.

【 授权许可】

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