Am J Psychiatry 157:1552-1562, October 2000
© 2000 American Psychiatric Association
Genetic Epidemiology of Major Depression: Review and Meta-Analysis
Patrick F. Sullivan, M.D., F.R.A.N.Z.C.P.,
Michael C. Neale, Ph.D., and
Kenneth S. Kendler, M.D.
Abstract
OBJECTIVE: The authors conducted a meta-analysis of relevant data from primary studies of the genetic epidemiology of major depression.METHOD: The authors searched MEDLINE and the reference lists of previous review articles to identify relevant primary studies. On the basis of a review of family, adoption, and twin studies that met specific inclusion criteria, the authors derived quantitative summary statistics. RESULTS: Five family studies met the inclusion criteria. The odds ratios for proband (subjects with major depression or comparison subjects) versus first-degree relative status (affected or unaffected with major depression) were homogeneous across the five studies (Mantel-Haenszel odds ratio=2.84, 95% CI=2.31–3.49). No adoption study met the inclusion criteria, but the results of two of the three reports were consistent with genetic influences on liability to major depression. Five twin studies met the inclusion criteria, and their statistical summation suggested that familial aggregation was due to additive genetic effects (point estimate of heritability of liability=37%, 95% CI=31%–42%), with a minimal contribution of environmental effects common to siblings (point estimate=0%, 95% CI=0%–5%), and substantial individual-specific environmental effects/measurement error (point estimate=63%, 95% CI=58%–67%). The literature suggests that recurrence best predicts the familial aggregation of major depression. CONCLUSIONS: Major depression is a familial disorder, and its familiality mostly or entirely results from genetic influences. Environmental influences specific to an individual are also etiologically significant. Major depression is a complex disorder that does not result from either genetic or environmental influences alone but rather from both. These findings are notably consistent across samples and methods and are likely to be generally applicable.
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|
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|
|
|
|
|
|
|
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164(11):
1693 - 1699.
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|
|
|
|
|
|
|
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21(5):
538 - 544.
[Abstract]
[PDF]
|
|
|
|
|
|
|
Z. N. Mannie, C. J. Harmer, and P. J. Cowen
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164(4):
617 - 621.
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|
|
|
|
|
|
|
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64(3):
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[Full Text]
[PDF]
|
|
|
|
|
|
|
P. McGuffin, S. Cohen, and J. Knight
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164(2):
195 - 197.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Holmans, M. M. Weissman, G. S. Zubenko, W. A. Scheftner, R. R. Crowe, J. R. DePaulo Jr., J. A. Knowles, W. N. Zubenko, K. Murphy-Eberenz, D. H. Marta, et al.
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164(2):
248 - 258.
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|
|
|
|
|
|
|
M. Alegria, N. Mulvaney-Day, M. Torres, A. Polo, Z. Cao, and G. Canino
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97(1):
68 - 75.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Essex, H. C. Kraemer, J. M. Armstrong, W. T. Boyce, H. H. Goldsmith, M. H. Klein, H. Woodward, and D. J. Kupfer
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Arch Gen Psychiatry,
November 1, 2006;
63(11):
1246 - 1256.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-L. Wong, F. Whelan, P. Deloukas, P. Whittaker, M. Delgado, R. M. Cantor, S. M. McCann, and J. Licinio
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103(41):
15124 - 15129.
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[Full Text]
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|
|
|
|
|
|
|
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October 1, 2006;
163(10):
1683 - 1694.
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|
|
|
|
|
|
|
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163(9):
1549 - 1553.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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163(9):
1554 - 1560.
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[Full Text]
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|
|
|
|
|
|
|
G. Zalsman, Y.-y. Huang, M. A. Oquendo, A. K. Burke, X.-z. Hu, D. A. Brent, S. P. Ellis, D. Goldman, and J. J. Mann
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163(9):
1588 - 1593.
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|
|
|
|
|
|
|
N. Jacobs, G. Kenis, F. Peeters, C. Derom, R. Vlietinck, and J. van Os
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63(9):
989 - 996.
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|
|
|
|
|
|
|
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15(16):
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|
|
|
|
|
|
|
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March 1, 2006;
68(2):
187 - 200.
[Abstract]
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|
|
|
|
|
|
|
K. S. Kendler, M. Gatz, C. O. Gardner, and N. L. Pedersen
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163(1):
109 - 114.
[Abstract]
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|
|
|
|
|
|
|
P. McGuffin, J. Knight, G. Breen, S. Brewster, P. R. Boyd, N. Craddock, M. Gill, A. Korszun, W. Maier, L. Middleton, et al.
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November 15, 2005;
14(22):
3337 - 3345.
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|
|
|
|
|
|
|
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May 1, 2005;
67(Supplement_1):
S26 - S28.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. S. Kendler
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Am J Psychiatry,
January 1, 2005;
162(1):
3 - 11.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. S. Kendler, C. O. Gardner, and C. A. Prescott
Toward a Comprehensive Developmental Model for Major Depression in Women
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January 1, 2005;
3(1):
83 - 97.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Weissman, P. Wickramaratne, Y. Nomura, V. Warner, H. Verdeli, D. J. Pilowsky, C. Grillon, and G. Bruder
Families at High and Low Risk for Depression: A 3-Generation Study
Arch Gen Psychiatry,
January 1, 2005;
62(1):
29 - 36.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. W. Nash, P. Huezo-Diaz, R. J. Williamson, A. Sterne, S. Purcell, F. Hoda, S. S. Cherny, G. R. Abecasis, M. Prince, J. A. Gray, et al.
Genome-wide linkage analysis of a composite index of neuroticism and mood-related scales in extreme selected sibships
Hum. Mol. Genet.,
October 1, 2004;
13(19):
2173 - 2182.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. T. Lynskey, A. L. Glowinski, A. A. Todorov, K. K. Bucholz, P. A. F. Madden, E. C. Nelson, D. J. Statham, N. G. Martin, and A. C. Heath
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Arch Gen Psychiatry,
October 1, 2004;
61(10):
1026 - 1032.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Korszun, V. Moskvina, S. Brewster, N. Craddock, F. Ferrero, M. Gill, I. R. Jones, L. A. Jones, W. Maier, O. Mors, et al.
Familiality of Symptom Dimensions in Depression
Arch Gen Psychiatry,
May 1, 2004;
61(5):
468 - 474.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. N. Klein, S. A. Shankman, P. M. Lewinsohn, P. Rohde, and J. R. Seeley
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Am J Psychiatry,
April 1, 2004;
161(4):
646 - 653.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. R. Uhl and R. W. Grow
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Arch Gen Psychiatry,
March 1, 2004;
61(3):
223 - 229.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Smith and D. H. R. Blackwood
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Advan. Psychiatr. Treat.,
January 1, 2004;
10(1):
4 - 12.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. F. Sullivan, K. S. Kendler, and M. C. Neale
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Arch Gen Psychiatry,
December 1, 2003;
60(12):
1187 - 1192.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
K. S. Kendler, C. A. Prescott, J. Myers, and M. C. Neale
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Arch Gen Psychiatry,
September 1, 2003;
60(9):
929 - 937.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. B. Keller
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JAMA,
June 18, 2003;
289(23):
3152 - 3160.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Farmer, A. Mahmood, K. Redman, T. Harris, S. Sadler, and P. McGuffin
A Sib-Pair Study of the Temperament and Character Inventory Scales in Major Depression
Arch Gen Psychiatry,
May 1, 2003;
60(5):
490 - 496.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. McCaffery, R. Niaura, J. F. Todaro, G. E. Swan, and D. Carmelli
Depressive Symptoms and Metabolic Risk in Adult Male Twins Enrolled in the National Heart, Lung, and Blood Institute Twin Study
Psychosom Med,
May 1, 2003;
65(3):
490 - 497.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. R. Merikangas and N. Risch
Will the Genomics Revolution Revolutionize Psychiatry?
Am J Psychiatry,
April 1, 2003;
160(4):
625 - 635.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Smith, W. Muir, D. Blackwood, G. Andrews, M. Szabo, and J. Burns
Genetics of early-onset depression * Authors' reply
The British Journal of Psychiatry,
April 1, 2003;
182(4):
363 - 364.
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Afari and D. Buchwald
Chronic Fatigue Syndrome: A Review
Am J Psychiatry,
February 1, 2003;
160(2):
221 - 236.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. I. Hudson, B. Mangweth, H. G. Pope Jr, C. De Col, A. Hausmann, S. Gutweniger, N. M. Laird, W. Biebl, and M. T. Tsuang
Family Study of Affective Spectrum Disorder
Arch Gen Psychiatry,
February 1, 2003;
60(2):
170 - 177.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. S. Kendler, C. O. Gardner, and C. A. Prescott
Toward a Comprehensive Developmental Model for Major Depression in Women
Am J Psychiatry,
July 1, 2002;
159(7):
1133 - 1145.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. S. Kendler
Twin Studies of Psychiatric Illness: An Update
Arch Gen Psychiatry,
November 1, 2001;
58(11):
1005 - 1014.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. F. Sullivan, L. J. Eaves, K. S. Kendler, and M. C. Neale
Genetic Case-Control Association Studies in Neuropsychiatry
Arch Gen Psychiatry,
November 1, 2001;
58(11):
1015 - 1024.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Farmer
Review: twin studies show that genes and individual environmental influences contribute to the aetiology of major depressionCommentary
Evid. Based Ment. Health,
May 1, 2001;
4(2):
62 - 62.
[Full Text]
[PDF]
|
|
|
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