TY - JOUR
T1 - Redefining Phenotypes to Advance Psychiatric Genetics: Implications From Hierarchical Taxonomy of Psychopathology
AU - Waszczuk, M.A.
AU - Eaton, N.R.
AU - Krueger, R.F.
AU - Shackman, A.J.
AU - Waldman, I.D.
AU - Zald, D.H.
AU - Lahey, B.B.
AU - Patrick, C.J.
AU - Conway, C.C.
AU - Ormel, J.
AU - Hyman, S.E.
AU - Fried, E.I.
AU - Forbes, M.K.
AU - Docherty, A.R.
AU - Althoff, R.R.
AU - Bach, B.
AU - Chmielewski, M.
AU - DeYoung, C.G.
AU - Forbush, K.T.
AU - Hallquist, M.
AU - Hopwood, C.J.
AU - Ivanova, M.Y.
AU - Jonas, K.G.
AU - Latzman, R.D.
AU - Markon, K.E.
AU - Mullins-Sweatt, S.N.
AU - Pincus, A.L.
AU - Reininghaus, U.
AU - South, S.C.
AU - Tackett, J.L.
AU - Watson, D.
AU - Wright, A.G.C.
AU - Kotov, R.
N1 - Publisher Copyright:
© 2019 American Psychological Association.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Genetic discovery in psychiatry and clinical psychology is hindered by suboptimal phenotypic definitions. We argue that the hierarchical, dimensional, and data-driven classification system proposed by the Hierarchical Taxonomy of Psychopathology (HiTOP) consortium provides a more effective approach to identifying genes that underlie mental disorders, and to studying psychiatric etiology, than current diagnostic categories. Specifically, genes are expected to operate at different levels of the HiTOP hierarchy, with some highly pleiotropic genes influencing higher order psychopathology (e.g., the general factor), whereas other genes conferring more specific risk for individual spectra (e.g., internalizing), subfactors (e.g., fear disorders), or narrow symptoms (e.g., mood instability). We propose that the HiTOP model aligns well with the current understanding of the higher order genetic structure of psychopathology that has emerged from a large body of family and twin studies. We also discuss the convergence between the HiTOP model and findings from recent molecular studies of psychopathology indicating broad genetic pleiotropy, such as cross-disorder SNP-based shared genetic covariance and polygenic risk scores, and we highlight molecular genetic studies that have successfully redefined phenotypes to enhance precision and statistical power. Finally, we suggest how to integrate a HiTOP approach into future molecular genetic research, including quantitative and hierarchical assessment tools for future data-collection and recommendations concerning phenotypic analyses.
AB - Genetic discovery in psychiatry and clinical psychology is hindered by suboptimal phenotypic definitions. We argue that the hierarchical, dimensional, and data-driven classification system proposed by the Hierarchical Taxonomy of Psychopathology (HiTOP) consortium provides a more effective approach to identifying genes that underlie mental disorders, and to studying psychiatric etiology, than current diagnostic categories. Specifically, genes are expected to operate at different levels of the HiTOP hierarchy, with some highly pleiotropic genes influencing higher order psychopathology (e.g., the general factor), whereas other genes conferring more specific risk for individual spectra (e.g., internalizing), subfactors (e.g., fear disorders), or narrow symptoms (e.g., mood instability). We propose that the HiTOP model aligns well with the current understanding of the higher order genetic structure of psychopathology that has emerged from a large body of family and twin studies. We also discuss the convergence between the HiTOP model and findings from recent molecular studies of psychopathology indicating broad genetic pleiotropy, such as cross-disorder SNP-based shared genetic covariance and polygenic risk scores, and we highlight molecular genetic studies that have successfully redefined phenotypes to enhance precision and statistical power. Finally, we suggest how to integrate a HiTOP approach into future molecular genetic research, including quantitative and hierarchical assessment tools for future data-collection and recommendations concerning phenotypic analyses.
KW - behavior genetics
KW - comorbidity
KW - deficit hyperactivity disorder
KW - dsm-iv criteria
KW - eating-disorders
KW - environmental risk-factors
KW - general factor
KW - genome-wide association
KW - major depression
KW - molecular genetics
KW - nosology
KW - personality-disorder
KW - polygenic risk
KW - population-based sample
KW - substance use disorders
KW - SUBSTANCE USE DISORDERS
KW - DSM-IV CRITERIA
KW - EATING-DISORDERS
KW - ENVIRONMENTAL RISK-FACTORS
KW - GENOME-WIDE ASSOCIATION
KW - PERSONALITY-DISORDER
KW - DEFICIT HYPERACTIVITY DISORDER
KW - MAJOR DEPRESSION
KW - POPULATION-BASED SAMPLE
KW - POLYGENIC RISK
U2 - 10.1037/abn0000486
DO - 10.1037/abn0000486
M3 - Article
C2 - 31804095
SN - 0021-843X
VL - 129
SP - 143
EP - 161
JO - Journal of Abnormal Psychology
JF - Journal of Abnormal Psychology
IS - 2
ER -