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Published in: BMC Psychiatry 1/2017

Open Access 01-12-2017 | Research article

Genetics of depressive symptoms in adolescence

Authors: Hannah Sallis, Jonathan Evans, Robyn Wootton, Eva Krapohl, Albertine J Oldehinkel, George Davey Smith, Lavinia Paternoster

Published in: BMC Psychiatry | Issue 1/2017

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Abstract

Background

Despite many attempts to understand the genetic architecture of depression, little progress has been made. The majority of these studies, however, have been carried out in adults and do not account for the potential influence of development.

Methods

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a longitudinal pregnancy cohort which recruited participants between April 1991 and December 1992. Analyses were replicated in two independent European cohorts. Genome-wide complex trait analysis (GCTA) software was used to investigate SNP-heritability (h2 SNP) of depression across adolescence, the role of puberty was investigated by stratifying these estimates according to pubertal onset. Genome-wide association studies were performed to identify genetic variants associated with depression at different stages of development.

Results

Heritability was estimated between the ages of 11 and 18 with sample sizes ranging from 3289 to 5480. Heritability was low with an apparent peak was found at age 13 (h2 = 0.17, p = 0.006). Confidence intervals around these estimates suggest an upper-bound to h2 SNP of around 30%. A variant located on chromosome 7 was found to be associated with depressive symptoms at age 13 in ALSPAC (rs138191010: β = 0.142, p = 2.51 × 10−8), although this was not replicated.

Conclusions

Although power is a potential limitation, the observed patterns provide interesting hypotheses surrounding the heritability of depression at different developmental stages. We found substantially lower estimates for depressive symptoms at age 11 (0.07) compared to those previously estimated in adults (0.21). We also found a peak in heritability at age 13. These findings suggest environmental factors are likely to be more important in the aetiology of depressive symptoms in early adolescence than in adulthood.
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Literature
1.
go back to reference Schizophrenia Working Group of the Psychiatric Genomics C. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511:421–7.CrossRef Schizophrenia Working Group of the Psychiatric Genomics C. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511:421–7.CrossRef
2.
go back to reference Major Depressive Disorder Working Group of the Psychiatric GC, Ripke S, Wray NR, Lewis CM, Hamilton SP, Weissman MM, et al. A mega-analysis of genome-wide association studies for major depressive disorder. Mol Psychiatry. 2013;18:497–511. Major Depressive Disorder Working Group of the Psychiatric GC, Ripke S, Wray NR, Lewis CM, Hamilton SP, Weissman MM, et al. A mega-analysis of genome-wide association studies for major depressive disorder. Mol Psychiatry. 2013;18:497–511.
3.
go back to reference Hyde CL, Nagle MW, Tian C, Chen X, Paciga SA, Wendland JR, et al. Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nature Research: Nat. Genet; 2016. Hyde CL, Nagle MW, Tian C, Chen X, Paciga SA, Wendland JR, et al. Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nature Research: Nat. Genet; 2016.
4.
go back to reference Okbay A, Baselmans BML, De Neve J-E. Turley P. Nivard MG: Fontana MA, et al. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nat. Genet; 2016. Okbay A, Baselmans BML, De Neve J-E. Turley P. Nivard MG: Fontana MA, et al. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nat. Genet; 2016.
5.
go back to reference Cai N, Bigdeli TB, Kretzschmar W, Li Y, Liang J, Song L, et al. Sparse whole-genome sequencing identifies two loci for major depressive disorder. Nature. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.; 2015;523:588–91. Cai N, Bigdeli TB, Kretzschmar W, Li Y, Liang J, Song L, et al. Sparse whole-genome sequencing identifies two loci for major depressive disorder. Nature. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.; 2015;523:588–91.
6.
go back to reference Ferentinos P, Koukounari A, Power R, Rivera M, Uher R, Craddock N, et al. Familiality and SNP heritability of age at onset and episodicity in major depressive disorder. Psychol Med Cambridge University Press. 2015;45:1–11. Ferentinos P, Koukounari A, Power R, Rivera M, Uher R, Craddock N, et al. Familiality and SNP heritability of age at onset and episodicity in major depressive disorder. Psychol Med Cambridge University Press. 2015;45:1–11.
7.
go back to reference Power RA, Keers R, Ng MY, Butler AW, Uher R, Cohen-Woods S, et al. Dissecting the genetic heterogeneity of depression through age at onset. Am J Med Genet B Neuropsychiatr Genet. 2012;159B:859–68.CrossRefPubMed Power RA, Keers R, Ng MY, Butler AW, Uher R, Cohen-Woods S, et al. Dissecting the genetic heterogeneity of depression through age at onset. Am J Med Genet B Neuropsychiatr Genet. 2012;159B:859–68.CrossRefPubMed
8.
go back to reference Shi J, Potash JB, Knowles JA, Weissman MM, Coryell W, Scheftner WA, et al. Genome-wide association study of recurrent early-onset major depressive disorder. Mol Psychiatry. 2011;16:193–201.CrossRefPubMed Shi J, Potash JB, Knowles JA, Weissman MM, Coryell W, Scheftner WA, et al. Genome-wide association study of recurrent early-onset major depressive disorder. Mol Psychiatry. 2011;16:193–201.CrossRefPubMed
9.
go back to reference Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry American Psychiatric Publishing. 2000;157:1552–62. Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry American Psychiatric Publishing. 2000;157:1552–62.
11.
go back to reference Cross-Disorder Group of the Psychiatric Genomics Consortium, Lee SH, Ripke S, Neale BM, Faraone S V, Purcell SM, et al. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat Genet. 2013;45:984–94. Cross-Disorder Group of the Psychiatric Genomics Consortium, Lee SH, Ripke S, Neale BM, Faraone S V, Purcell SM, et al. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat Genet. 2013;45:984–94.
12.
go back to reference Nivard MG, Dolan CV, Kendler KS, Kan KJ, Willemsen G, van Beijsterveldt CE, et al. Stability in symptoms of anxiety and depression as a function of genotype and environment: a longitudinal twin study from ages 3 to 63 years. Psychol Med. 2015;45:1039–49.CrossRefPubMed Nivard MG, Dolan CV, Kendler KS, Kan KJ, Willemsen G, van Beijsterveldt CE, et al. Stability in symptoms of anxiety and depression as a function of genotype and environment: a longitudinal twin study from ages 3 to 63 years. Psychol Med. 2015;45:1039–49.CrossRefPubMed
13.
go back to reference Thapar A, Rice F. Twin studies in pediatric depression. Child Adolesc Psychiatr Clin N Am. 2006;15:869–81. viiiCrossRefPubMed Thapar A, Rice F. Twin studies in pediatric depression. Child Adolesc Psychiatr Clin N Am. 2006;15:869–81. viiiCrossRefPubMed
14.
go back to reference Scourfield J, Rice F, Thapar A, Harold GT, Martin N, McGuffin P. Depressive symptoms in children and adolescents: changing aetiological influences with development. J Child Psychol Psychiatry. 2003;44:968–76.CrossRefPubMed Scourfield J, Rice F, Thapar A, Harold GT, Martin N, McGuffin P. Depressive symptoms in children and adolescents: changing aetiological influences with development. J Child Psychol Psychiatry. 2003;44:968–76.CrossRefPubMed
15.
go back to reference Rice F, Harold GT, Thapar A. Assessing the effects of age, sex and shared environment on the genetic aetiology of depression in childhood and adolescence. J Child Psychol Psychiatry. 2002;43:1039–51.CrossRefPubMed Rice F, Harold GT, Thapar A. Assessing the effects of age, sex and shared environment on the genetic aetiology of depression in childhood and adolescence. J Child Psychol Psychiatry. 2002;43:1039–51.CrossRefPubMed
16.
go back to reference Rice F. Genetics of childhood and adolescent depression: insights into etiological heterogeneity and challenges for future genomic research. Genome Med. 2010;2:68.CrossRefPubMedPubMedCentral Rice F. Genetics of childhood and adolescent depression: insights into etiological heterogeneity and challenges for future genomic research. Genome Med. 2010;2:68.CrossRefPubMedPubMedCentral
17.
go back to reference Silberg J, Pickles A, Rutter M, Hewitt J, Simonoff E, Maes H, et al. The influence of genetic factors and life stress on depression among adolescent girls. Arch Gen Psychiatry. 1999;56:225–32.CrossRefPubMed Silberg J, Pickles A, Rutter M, Hewitt J, Simonoff E, Maes H, et al. The influence of genetic factors and life stress on depression among adolescent girls. Arch Gen Psychiatry. 1999;56:225–32.CrossRefPubMed
19.
go back to reference Angold A, Costello EJ, Worthman CM. Puberty and depression: the roles of age, pubertal status and pubertal timing. Psychol Med. 1998;28:51–61.CrossRefPubMed Angold A, Costello EJ, Worthman CM. Puberty and depression: the roles of age, pubertal status and pubertal timing. Psychol Med. 1998;28:51–61.CrossRefPubMed
20.
go back to reference Joinson C, Heron J, Lewis G, Croudace T, Araya R. Timing of menarche and depressive symptoms in adolescent girls from a UK cohort. Br J Psychiatry. 2011;198:17–23, NaN-2. Joinson C, Heron J, Lewis G, Croudace T, Araya R. Timing of menarche and depressive symptoms in adolescent girls from a UK cohort. Br J Psychiatry. 2011;198:17–23, NaN-2.
21.
go back to reference Rudolph KD, Troop-Gordon W, Lambert SF, Natsuaki MN. Long-term consequences of pubertal timing for youth depression: identifying personal and contextual pathways of risk. Dev Psychopathol. 2014;26:1423–44.CrossRefPubMedPubMedCentral Rudolph KD, Troop-Gordon W, Lambert SF, Natsuaki MN. Long-term consequences of pubertal timing for youth depression: identifying personal and contextual pathways of risk. Dev Psychopathol. 2014;26:1423–44.CrossRefPubMedPubMedCentral
22.
go back to reference Whittle S, Yücel M, Lorenzetti V, Byrne ML, Simmons JG, Wood SJ, et al. Pituitary volume mediates the relationship between pubertal timing and depressive symptoms during adolescence. Psychoneuroendocrinology. 2012;37:881–91.CrossRefPubMed Whittle S, Yücel M, Lorenzetti V, Byrne ML, Simmons JG, Wood SJ, et al. Pituitary volume mediates the relationship between pubertal timing and depressive symptoms during adolescence. Psychoneuroendocrinology. 2012;37:881–91.CrossRefPubMed
23.
go back to reference Goodyer IM, Herbert J, Altham PM. Adrenal steroid secretion and major depression in 8- to 16-year-olds, III. Influence of cortisol/DHEA ratio at presentation on subsequent rates of disappointing life events and persistent major depression. Psychol. Med. 1998;28:265–73. Goodyer IM, Herbert J, Altham PM. Adrenal steroid secretion and major depression in 8- to 16-year-olds, III. Influence of cortisol/DHEA ratio at presentation on subsequent rates of disappointing life events and persistent major depression. Psychol. Med. 1998;28:265–73.
24.
go back to reference Mendle J, Turkheimer E, Emery RE. Detrimental psychological outcomes associated with early pubertal timing in adolescent girls. Dev Rev. 2007;27:151–71.CrossRefPubMedPubMedCentral Mendle J, Turkheimer E, Emery RE. Detrimental psychological outcomes associated with early pubertal timing in adolescent girls. Dev Rev. 2007;27:151–71.CrossRefPubMedPubMedCentral
25.
go back to reference Fraser A, Macdonald-Wallis C, Tilling K, Boyd A, Golding J, Davey Smith G, et al. Cohort profile: the Avon longitudinal study of parents and children: ALSPAC mothers cohort. Int J Epidemiol. 2013;42:97–110.CrossRefPubMed Fraser A, Macdonald-Wallis C, Tilling K, Boyd A, Golding J, Davey Smith G, et al. Cohort profile: the Avon longitudinal study of parents and children: ALSPAC mothers cohort. Int J Epidemiol. 2013;42:97–110.CrossRefPubMed
26.
go back to reference Boyd A, Golding J, Macleod J, Lawlor DA, Fraser A, Henderson J, et al. Cohort profile: the “children of the 90s”--the index offspring of the Avon longitudinal study of parents and children. Int J Epidemiol. 2013;42:111–27.CrossRefPubMed Boyd A, Golding J, Macleod J, Lawlor DA, Fraser A, Henderson J, et al. Cohort profile: the “children of the 90s”--the index offspring of the Avon longitudinal study of parents and children. Int J Epidemiol. 2013;42:111–27.CrossRefPubMed
27.
go back to reference Angold A, Costello EJ, Messer SC, Pickles A. Development of a short questionnaire for use in epidemiological studies of depression in children and adolescents. Int J Methods Psychiatr Res US: John Wiley & Sons. 1995;5:237–49. Angold A, Costello EJ, Messer SC, Pickles A. Development of a short questionnaire for use in epidemiological studies of depression in children and adolescents. Int J Methods Psychiatr Res US: John Wiley & Sons. 1995;5:237–49.
30.
go back to reference Visscher PM, Hemani G, Vinkhuyzen AA, Chen GB, Lee SH, Wray NR, et al. Statistical power to detect genetic (co)variance of complex traits using SNP data in unrelated samples. PLoS Genet. 2014;10:e1004269.CrossRefPubMedPubMedCentral Visscher PM, Hemani G, Vinkhuyzen AA, Chen GB, Lee SH, Wray NR, et al. Statistical power to detect genetic (co)variance of complex traits using SNP data in unrelated samples. PLoS Genet. 2014;10:e1004269.CrossRefPubMedPubMedCentral
31.
go back to reference Marchini J, Howie B, Myers S, McVean G, Donnelly P. A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet Nature Publishing Group. 2007;39:906–13.CrossRef Marchini J, Howie B, Myers S, McVean G, Donnelly P. A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet Nature Publishing Group. 2007;39:906–13.CrossRef
32.
go back to reference Huisman M, Oldehinkel AJ, de Winter A, Minderaa RB, de Bildt A, Huizink AC, et al. Cohort profile: the Dutch “TRacking adolescents” individual lives’ survey’. TRAILS Int J Epidemiol. 2008;37:1227–35.CrossRefPubMed Huisman M, Oldehinkel AJ, de Winter A, Minderaa RB, de Bildt A, Huizink AC, et al. Cohort profile: the Dutch “TRacking adolescents” individual lives’ survey’. TRAILS Int J Epidemiol. 2008;37:1227–35.CrossRefPubMed
33.
go back to reference Oldehinkel AJ, Rosmalen JG, Buitelaar JK, Hoek HW, Ormel J, Raven D, et al. Cohort Profile Update: the TRacking Adolescents’ Individual Lives Survey (TRAILS). Int. J. Epidemiol. 2015;44:76–76n. Oldehinkel AJ, Rosmalen JG, Buitelaar JK, Hoek HW, Ormel J, Raven D, et al. Cohort Profile Update: the TRacking Adolescents’ Individual Lives Survey (TRAILS). Int. J. Epidemiol. 2015;44:76–76n.
34.
go back to reference Haworth CMA, Davis OSP, Plomin R. Twins early development study (TEDS): a genetically sensitive investigation of cognitive and behavioral development from childhood to young adulthood. Twin res. Hum. Genet. Cambridge University Press. 2013;16:117–25. Haworth CMA, Davis OSP, Plomin R. Twins early development study (TEDS): a genetically sensitive investigation of cognitive and behavioral development from childhood to young adulthood. Twin res. Hum. Genet. Cambridge University Press. 2013;16:117–25.
Metadata
Title
Genetics of depressive symptoms in adolescence
Authors
Hannah Sallis
Jonathan Evans
Robyn Wootton
Eva Krapohl
Albertine J Oldehinkel
George Davey Smith
Lavinia Paternoster
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2017
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/s12888-017-1484-y

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