Kenneth S Kendler1, Henrik Ohlsson1, Paul Lichtenstein1, Jan Sundquist1, Kristina Sundquist1. 1. From the Department of Psychiatry and the Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond; the Center for Primary Health Care Research, Lund University, Malmö, Sweden; and the Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
Abstract
OBJECTIVE: The authors examined the heritability of treated major depression in a twin and full/half-sibling design, to describe key genetic epidemiological features of major depression and to determine which clinical indices of genetic liability optimally predict risk of depression in relatives. METHOD: The authors examined all treated cases of major depression in Sweden recorded in inpatient, specialist, and primary care registries and, using OpenMx, estimated the etiologic role of genetic and environmental factors from monozygotic and dizygotic twin pairs and full and half siblings reared together and apart (total N=1,718,863 pairs). Eight indices of genetic risk were examined in 875,010 proband-relative pairs. RESULTS: The heritability of major depression in men and women was estimated at 0.41 (95% CI=0.21, 0.49) and 0.49 (95% CI=0.31, 0.56), respectively, in the twin design and 0.36 (95% CI=0.31, 0.38) and 0.51 (95% CI=0.51, 0.53), respectively, in the independent full/half-sibling design. The best estimate of the correlation in genetic effects across sexes was 0.89 (95% CI=0.87, 0.91). The results also showed evidence of modest shared environmental effects (0.02-0.05). Seven of the eight indices predicted risk for major depression in relatives, with stronger effects in those more closely related. The strongest indices were early age at onset, recurrence, comorbid anxiety disorder, and measures of clinical severity. CONCLUSIONS: In a large national sample, the heritability of major depression was similar when estimated from twin and full/half-sibling designs. The heritability of major depression was greater in women than in men, with the two sexes sharing most but not all genetic risk factors. In affected individuals, genetic risk for major depression could be meaningfully assessed from commonly available clinical indices.
OBJECTIVE: The authors examined the heritability of treated major depression in a twin and full/half-sibling design, to describe key genetic epidemiological features of major depression and to determine which clinical indices of genetic liability optimally predict risk of depression in relatives. METHOD: The authors examined all treated cases of major depression in Sweden recorded in inpatient, specialist, and primary care registries and, using OpenMx, estimated the etiologic role of genetic and environmental factors from monozygotic and dizygotic twin pairs and full and half siblings reared together and apart (total N=1,718,863 pairs). Eight indices of genetic risk were examined in 875,010 proband-relative pairs. RESULTS: The heritability of major depression in men and women was estimated at 0.41 (95% CI=0.21, 0.49) and 0.49 (95% CI=0.31, 0.56), respectively, in the twin design and 0.36 (95% CI=0.31, 0.38) and 0.51 (95% CI=0.51, 0.53), respectively, in the independent full/half-sibling design. The best estimate of the correlation in genetic effects across sexes was 0.89 (95% CI=0.87, 0.91). The results also showed evidence of modest shared environmental effects (0.02-0.05). Seven of the eight indices predicted risk for major depression in relatives, with stronger effects in those more closely related. The strongest indices were early age at onset, recurrence, comorbid anxiety disorder, and measures of clinical severity. CONCLUSIONS: In a large national sample, the heritability of major depression was similar when estimated from twin and full/half-sibling designs. The heritability of major depression was greater in women than in men, with the two sexes sharing most but not all genetic risk factors. In affected individuals, genetic risk for major depression could be meaningfully assessed from commonly available clinical indices.
Authors: Amy E Miles; Fernanda C Dos Santos; Enda M Byrne; Miguel E Renteria; Andrew M McIntosh; Mark J Adams; Giorgio Pistis; Enrique Castelao; Martin Preisig; Bernhard T Baune; K Oliver Schubert; Cathryn M Lewis; Lisa A Jones; Ian Jones; Rudolf Uher; Jordan W Smoller; Roy H Perlis; Douglas F Levinson; James B Potash; Myrna M Weissman; Jianxin Shi; Glyn Lewis; Brenda W J H Penninx; Dorret I Boomsma; Steven P Hamilton; Etienne Sibille; Ahmad R Hariri; Yuliya S Nikolova Journal: Neuropsychopharmacology Date: 2021-09-29 Impact factor: 7.853
Authors: Alexis C Edwards; Henrik Ohlsson; Eve Mościcki; Casey Crump; Jan Sundquist; Paul Lichtenstein; Kenneth S Kendler; Kristina Sundquist Journal: Am J Psychiatry Date: 2021-07-14 Impact factor: 18.112