Abstract
Original language | English |
---|---|
Pages (from-to) | 2646-2656 |
Journal | Psychological Medicine |
Volume | 49 |
Issue number | 16 |
DOIs | |
Publication status | Published - 2019 |
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Unraveling the genetic architecture of major depressive disorder : Merits and pitfalls of the approaches used in genome-wide association studies. / Schwabe, I.; Milaneschi, Y.; Gerring, Z.; Sullivan, P. F.; Schulte, E.; Suppli, N. P.; Thorp, J. G.; Derks, E. M.; Middeldorp, C. M.
In: Psychological Medicine, Vol. 49, No. 16, 2019, p. 2646-2656.Research output: Contribution to journal › Article › Scientific › peer-review
TY - JOUR
T1 - Unraveling the genetic architecture of major depressive disorder
T2 - Merits and pitfalls of the approaches used in genome-wide association studies
AU - Schwabe, I.
AU - Milaneschi, Y.
AU - Gerring, Z.
AU - Sullivan, P. F.
AU - Schulte, E.
AU - Suppli, N. P.
AU - Thorp, J. G.
AU - Derks, E. M.
AU - Middeldorp, C. M.
PY - 2019
Y1 - 2019
N2 - To identify genetic risk loci for major depressive disorder (MDD), two broad study design approaches have been applied: (1) to maximize sample size by combining data from different phenotype assessment modalities (e.g. clinical interview, self-report questionnaires) and (2) to reduce phenotypic heterogeneity through selecting more homogenous MDD subtypes. The value of these strategies has been debated. In this review, we summarize the most recent findings of large genomic studies that applied these approaches, and we highlight the merits and pitfalls of both approaches with particular attention to methodological and psychometric issues. We also discuss the results of analyses that investigated the heterogeneity of MDD. We conclude that both study designs are essential for further research. So far, increasing sample size has led to the identification of a relatively high number of genomic loci linked to depression. However, part of the identified variants may be related to a phenotype common to internalizing disorders and related traits. As such, samples containing detailed clinical information are needed to dissect depression heterogeneity and enable the potential identification of variants specific to a more restricted MDD phenotype. A balanced portfolio reconciling both study design approaches is the optimal approach to progress further in unraveling the genetic architecture of depression.
AB - To identify genetic risk loci for major depressive disorder (MDD), two broad study design approaches have been applied: (1) to maximize sample size by combining data from different phenotype assessment modalities (e.g. clinical interview, self-report questionnaires) and (2) to reduce phenotypic heterogeneity through selecting more homogenous MDD subtypes. The value of these strategies has been debated. In this review, we summarize the most recent findings of large genomic studies that applied these approaches, and we highlight the merits and pitfalls of both approaches with particular attention to methodological and psychometric issues. We also discuss the results of analyses that investigated the heterogeneity of MDD. We conclude that both study designs are essential for further research. So far, increasing sample size has led to the identification of a relatively high number of genomic loci linked to depression. However, part of the identified variants may be related to a phenotype common to internalizing disorders and related traits. As such, samples containing detailed clinical information are needed to dissect depression heterogeneity and enable the potential identification of variants specific to a more restricted MDD phenotype. A balanced portfolio reconciling both study design approaches is the optimal approach to progress further in unraveling the genetic architecture of depression.
U2 - 10.1017/S0033291719002502
DO - 10.1017/S0033291719002502
M3 - Article
VL - 49
SP - 2646
EP - 2656
JO - Psychological Medicine
JF - Psychological Medicine
SN - 0033-2917
IS - 16
ER -