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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 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 - Psychol Med (2015)

Bottom Line: 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.Significant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07).The described statistical framework could be useful in future analyses.

View Article: PubMed Central - PubMed

Affiliation: MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London,London,UK.

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.

No MeSH data available.


Related in: MedlinePlus

Frequency distributions (histograms) of (a) age, (b) age at onset, (c) episode count and (d) episode frequency in genotyped cases (merged RADIANT and GSK Munich samples).
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fig01: Frequency distributions (histograms) of (a) age, (b) age at onset, (c) episode count and (d) episode frequency in genotyped cases (merged RADIANT and GSK Munich samples).

Mentions: Demographic and clinical characteristics of DeNt siblings and genotyped cases (RADIANT and GSK Munich samples and their merge) are shown in Table 2 and Supplementary Table S1. Frequency distributions (histograms) of age, AAO, episode count and episode frequency in genotyped cases (Fig. 1, Supplementary Fig. S2) and in DeNT siblings (Supplementary Fig. S1) were plotted.Fig. 1.


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 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 - Psychol Med (2015)

Frequency distributions (histograms) of (a) age, (b) age at onset, (c) episode count and (d) episode frequency in genotyped cases (merged RADIANT and GSK Munich samples).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4462162&req=5

fig01: Frequency distributions (histograms) of (a) age, (b) age at onset, (c) episode count and (d) episode frequency in genotyped cases (merged RADIANT and GSK Munich samples).
Mentions: Demographic and clinical characteristics of DeNt siblings and genotyped cases (RADIANT and GSK Munich samples and their merge) are shown in Table 2 and Supplementary Table S1. Frequency distributions (histograms) of age, AAO, episode count and episode frequency in genotyped cases (Fig. 1, Supplementary Fig. S2) and in DeNT siblings (Supplementary Fig. S1) were plotted.Fig. 1.

Bottom Line: 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.Significant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07).The described statistical framework could be useful in future analyses.

View Article: PubMed Central - PubMed

Affiliation: MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London,London,UK.

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.

No MeSH data available.


Related in: MedlinePlus