Familiality and SNP heritability of age at onset and episodicity in major depressive disorder

Research output: Contribution to journalArticlepeer-review

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Familiality and SNP heritability of age at onset and episodicity in major depressive disorder. / Ferentinos, P.; Koukounari, A.; Power, R.; Rivera, M.; Uher, R.; Craddock, N.; Owen, M. J.; Korszun, A.; Jones, Lisa; Jones, I.; Gill, M.; Rice, J. P.; Ising, M.; Maier, W.; Mors, O.; Rietschel, M.; Preisig, M.; Binder, E. B.; Aitchison, K. J.; Mendlewicz, J.; Souery, D.; Hauser, J.; Henigsberg, N.; Breen, G.; Craig, I. W.; Farmer, A. E.; Müller-myhsok, B.; Mcguffin, P.; Lewis, C. M.

In: Psychological Medicine, Vol. 45, No. 10, 01.07.2015, p. 2215-2225.

Research output: Contribution to journalArticlepeer-review

Harvard

Ferentinos, P, Koukounari, A, Power, R, Rivera, M, Uher, R, Craddock, N, Owen, MJ, Korszun, A, Jones, L, Jones, I, Gill, M, Rice, JP, Ising, M, Maier, W, Mors, O, Rietschel, M, Preisig, M, Binder, EB, Aitchison, KJ, Mendlewicz, J, Souery, D, Hauser, J, Henigsberg, N, Breen, G, Craig, IW, Farmer, AE, Müller-myhsok, B, Mcguffin, P & Lewis, CM 2015, 'Familiality and SNP heritability of age at onset and episodicity in major depressive disorder', Psychological Medicine, vol. 45, no. 10, pp. 2215-2225. https://doi.org/10.1017/S0033291715000215

APA

Ferentinos, P., Koukounari, A., Power, R., Rivera, M., Uher, R., Craddock, N., Owen, M. J., Korszun, A., Jones, L., Jones, I., Gill, M., Rice, J. P., Ising, M., Maier, W., Mors, O., Rietschel, M., Preisig, M., Binder, E. B., Aitchison, K. J., ... Lewis, C. M. (2015). Familiality and SNP heritability of age at onset and episodicity in major depressive disorder. Psychological Medicine, 45(10), 2215-2225. https://doi.org/10.1017/S0033291715000215

Vancouver

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. Psychological Medicine. 2015 Jul 1;45(10):2215-2225. https://doi.org/10.1017/S0033291715000215

Author

Ferentinos, P. ; Koukounari, A. ; Power, R. ; Rivera, M. ; Uher, R. ; Craddock, N. ; Owen, M. J. ; Korszun, A. ; Jones, Lisa ; Jones, I. ; Gill, M. ; Rice, J. P. ; Ising, M. ; Maier, W. ; Mors, O. ; Rietschel, M. ; Preisig, M. ; Binder, E. B. ; Aitchison, K. J. ; Mendlewicz, J. ; Souery, D. ; Hauser, J. ; Henigsberg, N. ; Breen, G. ; Craig, I. W. ; Farmer, A. E. ; Müller-myhsok, B. ; Mcguffin, P. ; Lewis, C. M. / Familiality and SNP heritability of age at onset and episodicity in major depressive disorder. In: Psychological Medicine. 2015 ; Vol. 45, No. 10. pp. 2215-2225.

Bibtex

@article{b8aaa650ed7143c49ff9b5fbfc7e2443,
title = "Familiality and SNP heritability of age at onset and episodicity in major depressive disorder",
abstract = "Background Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) and recurrence/episodicity. Yet, evidence on whether these subphenotypes are familial or heritable is scarce. The aims of this study are to investigate the familiality of AAO and episode frequency in MDD and to assess the proportion of their variance explained by common single nucleotide polymorphisms (SNP heritability).Method For investigating familiality, we used 691 families with 2–5 full siblings with recurrent MDD from the DeNt study. We fitted (square root) AAO and episode count in a linear and a negative binomial mixed model, respectively, with family as random effect and adjusting for sex, age and center. The strength of familiality was assessed with intraclass correlation coefficients (ICC). For estimating SNP heritabilities, we used 3468 unrelated MDD cases from the RADIANT and GSK Munich studies. After similarly adjusting for covariates, derived residuals were used with the GREML method in GCTA (genome-wide complex trait analysis) software.Results Significant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07). We calculated from respective ICC estimates the maximal additive heritability of AAO (0.56) and episodicity (0.15). SNP heritability of AAO was 0.17 (p = 0.04); analysis was underpowered for calculating SNP heritability of episodicity.Conclusions AAO and episodicity aggregate in families to a moderate and small degree, respectively. AAO is under stronger additive genetic control than episodicity. Larger samples are needed to calculate the SNP heritability of episodicity. The described statistical framework could be useful in future analyses.",
keywords = "Age at onset, episodicity, familiality, GCTA, heritability, major depression",
author = "P. Ferentinos and A. Koukounari and R. Power and M. Rivera and R. Uher and N. Craddock and Owen, {M. J.} and A. Korszun and Lisa Jones and I. Jones and M. Gill and Rice, {J. P.} and M. Ising and W. Maier and O. Mors and M. Rietschel and M. Preisig and Binder, {E. B.} and Aitchison, {K. J.} and J. Mendlewicz and D. Souery and J. Hauser and N. Henigsberg and G. Breen and Craig, {I. W.} and Farmer, {A. E.} and B. M{\"u}ller-myhsok and P. Mcguffin and Lewis, {C. M.}",
year = "2015",
month = jul,
day = "1",
doi = "10.1017/S0033291715000215",
language = "English",
volume = "45",
pages = "2215--2225",
journal = "Psychological Medicine",
issn = "0033-2917",
publisher = "Cambridge University Press",
number = "10",

}

RIS

TY - JOUR

T1 - Familiality and SNP heritability of age at onset and episodicity in major depressive disorder

AU - Ferentinos, P.

AU - Koukounari, A.

AU - Power, R.

AU - Rivera, M.

AU - Uher, R.

AU - Craddock, N.

AU - Owen, M. J.

AU - Korszun, A.

AU - Jones, Lisa

AU - Jones, I.

AU - Gill, M.

AU - Rice, J. P.

AU - Ising, M.

AU - Maier, W.

AU - Mors, O.

AU - Rietschel, M.

AU - Preisig, M.

AU - Binder, E. B.

AU - Aitchison, K. J.

AU - Mendlewicz, J.

AU - Souery, D.

AU - Hauser, J.

AU - Henigsberg, N.

AU - Breen, G.

AU - Craig, I. W.

AU - Farmer, A. E.

AU - Müller-myhsok, B.

AU - Mcguffin, P.

AU - Lewis, C. M.

PY - 2015/7/1

Y1 - 2015/7/1

N2 - Background Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) and recurrence/episodicity. Yet, evidence on whether these subphenotypes are familial or heritable is scarce. The aims of this study are to investigate the familiality of AAO and episode frequency in MDD and to assess the proportion of their variance explained by common single nucleotide polymorphisms (SNP heritability).Method For investigating familiality, we used 691 families with 2–5 full siblings with recurrent MDD from the DeNt study. We fitted (square root) AAO and episode count in a linear and a negative binomial mixed model, respectively, with family as random effect and adjusting for sex, age and center. The strength of familiality was assessed with intraclass correlation coefficients (ICC). For estimating SNP heritabilities, we used 3468 unrelated MDD cases from the RADIANT and GSK Munich studies. After similarly adjusting for covariates, derived residuals were used with the GREML method in GCTA (genome-wide complex trait analysis) software.Results Significant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07). We calculated from respective ICC estimates the maximal additive heritability of AAO (0.56) and episodicity (0.15). SNP heritability of AAO was 0.17 (p = 0.04); analysis was underpowered for calculating SNP heritability of episodicity.Conclusions AAO and episodicity aggregate in families to a moderate and small degree, respectively. AAO is under stronger additive genetic control than episodicity. Larger samples are needed to calculate the SNP heritability of episodicity. The described statistical framework could be useful in future analyses.

AB - Background Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) and recurrence/episodicity. Yet, evidence on whether these subphenotypes are familial or heritable is scarce. The aims of this study are to investigate the familiality of AAO and episode frequency in MDD and to assess the proportion of their variance explained by common single nucleotide polymorphisms (SNP heritability).Method For investigating familiality, we used 691 families with 2–5 full siblings with recurrent MDD from the DeNt study. We fitted (square root) AAO and episode count in a linear and a negative binomial mixed model, respectively, with family as random effect and adjusting for sex, age and center. The strength of familiality was assessed with intraclass correlation coefficients (ICC). For estimating SNP heritabilities, we used 3468 unrelated MDD cases from the RADIANT and GSK Munich studies. After similarly adjusting for covariates, derived residuals were used with the GREML method in GCTA (genome-wide complex trait analysis) software.Results Significant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07). We calculated from respective ICC estimates the maximal additive heritability of AAO (0.56) and episodicity (0.15). SNP heritability of AAO was 0.17 (p = 0.04); analysis was underpowered for calculating SNP heritability of episodicity.Conclusions AAO and episodicity aggregate in families to a moderate and small degree, respectively. AAO is under stronger additive genetic control than episodicity. Larger samples are needed to calculate the SNP heritability of episodicity. The described statistical framework could be useful in future analyses.

KW - Age at onset

KW - episodicity

KW - familiality

KW - GCTA

KW - heritability

KW - major depression

U2 - 10.1017/S0033291715000215

DO - 10.1017/S0033291715000215

M3 - Article

VL - 45

SP - 2215

EP - 2225

JO - Psychological Medicine

JF - Psychological Medicine

SN - 0033-2917

IS - 10

ER -