A Structural Approach to the Familial Coaggregation of Disorders
Abstract
The demonstration that 2 disorders coaggregate in families is often the first step in the exploration of genetic factors common to the 2 disorders. Previous methods of analyzing familial coaggregation have used either (1) a typical measure of association (eg, the odds ratio) between a disorder in an individual and another disorder in family members, or (2) a linear structural equation model (SEM). The association method accommodates case-control sampling of families, but may not assess the causal effect of interest because it is not based on an underlying causal model. The SEM method is based on a causal model, but cannot easily accommodate case-control sampling or direct effects of 1 disorder on the other within individuals. We develop a new method of analyzing coaggregation based on directed acyclic graphs. Because this method is a generalization of structural equation models and uses measures of association that accommodate case-control sampling and direct effects, it combines the strengths of both previous methods. In the absence of direct effects between disorders, our approach provides a valid estimate of the causal coaggregation effect. In the presence of direct effects, our approach provides an upper-bound estimate and (assuming additive linear effects of latent familial and nonfamilial factors) a lower-bound estimate of the causal coaggregation effect. For illustration, we applied our method to a family study of binge eating disorder and bipolar disorder.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Hudson et al. applied these results in a study of familial coaggregation of diseases.
“Hudson et al. (2008) apply these results productively in a study of familial coaggregation of diseases.”
From Endogenous Selection Bias: The Problem of Conditioning on a Collider Variable (2014) · cites this paper as Hudson et al. 2008
Cites
Introduction to Quantitative Genetics.
Edwards, A. W. F., & Falconer, D. S. (1982) · Biometrics · doi:10.2307/2529912 · Cited by 21,447 · see citing works
Marginal Structural Models and Causal Inference in Epidemiology
Robins, J. M., Hernán, M. Á., & Brumback, B. (2000) · Epidemiology · doi:10.1097/00001648-200009000-00011 · Cited by 5,581 · see citing works
Self-citationMethodology for Genetic Studies of Twins and Families
Neale, M. C., & Cardon, L. R. (1992) · doi:10.1007/978-94-015-8018-2 · Cited by 4,005 · see citing works
Introduction to quantitative genetics
Falconer, D. S. (1960) · Helmholtz Centre for Ocean Research Kiel (GEOMAR) · Cited by 3,205 · see citing works
Martuza, V. R., & Kenny, D. A. (1981) · Educational Researcher · doi:10.2307/1175080 · Cited by 2,034 · see citing works
Introduction to Quantitative Genetics.
Bodmer, W. F., & Falconer, D. S. (1961) · Biometrics · doi:10.2307/2528001 · Cited by 1,873 · see citing works
Introduction to Quantitative Genetics
Byrd, W. P. (1961) · Agronomy Journal · doi:10.2134/agronj1961.00021962005300010026x · Cited by 1,583 · see citing works
Confounding and Collapsibility in Causal Inference
Greenland, S., Pearl, J., & Robins, J. M. (1999) · Statistical Science · doi:10.1214/ss/1009211805 · Cited by 933 · see citing works
Quantifying Biases in Causal Models: Classical Confounding vs Collider-Stratification Bias
Greenland, S. (2003) · Epidemiology · doi:10.1097/01.ede.0000042804.12056.6c · Cited by 810 · see citing works
Major Depression and Generalized Anxiety Disorder: Same Genes, (Partly) Different Environments?
Kendler, K. S. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820090044008 · Cited by 773 · see citing works
Family, twin, and adoption studies of bipolar disorder
Smoller, J. W., & Finn, C. T. (2003) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.20013 · Cited by 714 · see citing works
The Structure of Genetic and Environmental Risk Factors for Anxiety Disorders in Men and Women
Hettema, J. M., Prescott, C. A., Myers, J., Neale, M. C., & Kendler, K. S. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.2.182 · Cited by 541 · see citing works
Marginal Structural Models to Estimate the Joint Causal Effect of Nonrandomized Treatments
Hernán, M. Á., Brumback, B., & Robins, J. M. (2001) · Journal of the American Statistical Association · doi:10.1198/016214501753168154 · Cited by 483 · see citing works
Self-citationModel Selection, Confounder Control, and Marginal Structural Models
Joffe, M. M., Have, T. R. T., Feldman, H. I., & Kimmel, S. E. (2004) · The American Statistician · doi:10.1198/000313004x5824 · Cited by 266 · see citing works
A Family Study of Alcohol Dependence
Nürnberger, J. I., Wiegand, R. E., Bucholz, K. K., O’Connor, S., Meyer, E. T., Reich, T., Rice, J. P., Schuckit, M. A., King, L. J., Petti, T. A., et al. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.12.1246 · Cited by 254 · see citing works
NESTADT, G., SAMUELS, J., RIDDLE, M. A., LIANG, K.-Y., BIENVENU, O. J., HOEHN-SARIC, R., GRADOS, M., & CULLEN, B. (2001) · Psychological Medicine · doi:10.1017/s0033291701003579 · Cited by 253 · see citing works
Testing hypotheses about direction of causation using cross-sectional family data
Heath, A. C., Kessler, R. C., Neale, M., Hewitt, J. K., Eaves, L., & Kendler, K. (1993) · Behavior Genetics · doi:10.1007/bf01067552 · Cited by 223 · see citing works
Basic issues in psychopathology
Rachman, S. (1994) · Behaviour Research and Therapy · doi:10.1016/0005-7967(94)90173-2 · Cited by 196 · see citing works
The Relationship Between Panic Disorder and Major Depression: A New Family Study
Weissman, M. M. (1993) · Archives of General Psychiatry · doi:10.1001/archpsyc.1993.01820220017003 · Cited by 196 · see citing works
A Direct Interview Family Study of Social Phobia
Fyer, A. J. (1993) · Archives of General Psychiatry · doi:10.1001/archpsyc.1993.01820160056007 · Cited by 195 · see citing works
Games, P. A. (1990) · The Journal of Experimental Education · doi:10.1080/00220973.1990.10806538 · Cited by 180 · see citing works
Psychiatric disorders: Problems of boundaries and comorbidity.
Klein, D. N., & Riso, L. P. (1993) · Cited by 177 · see citing works
Binge-eating disorder as a distinct familial phenotype in obese individuals.
Hudson, J., Lalonde, J., Berry, J. M., Pindyck, L. J., Bulik, C., Crow, S., McElroy, S., Laird, N., Tsuang, M., Walsh, B., et al. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.3.313 · Cited by 176 · see citing works
Self-citationPsychiatric disorders in the first-degree relatives of probands with bulimia nervosa
Kassett, J. A., Gershon, E. S., Maxwell, M. E., Guroff, J. J., Kazuba, D. M., Smith, A. L., Brandt, H., & Jimerson, D. C. (1989) · American Journal of Psychiatry · doi:10.1176/ajp.146.11.1468 · Cited by 174 · see citing works
Javaras, K. N., Laird, N. M., Reichborn‐Kjennerud, T., Bulik, C. M., Pope, H. G., & Hudson, J. I. (2008) · International Journal of Eating Disorders · doi:10.1002/eat.20484 · Cited by 172 · see citing works
Self-citationA controlled family history study of bulimia
Hudson, J. I., Pope, H. G., Jonas, J. M., Yurgelun-Todd, D., & Frankenburg, F. R. (1987) · Psychological Medicine · doi:10.1017/s0033291700000684 · Cited by 137 · see citing works
Self-citationDuffy, D. L., & Martin, N. G. (1994) · Genetic Epidemiology · doi:10.1002/gepi.1370110606 · Cited by 131 · see citing works
Signed Directed Acyclic Graphs for Causal Inference
VanderWeele, T. J., & Robins, J. M. (2010) · Journal of the Royal Statistical Society Series B (Statistical Methodology) · doi:10.1111/j.1467-9868.2009.00728.x · Cited by 107 · see citing works
Self-citationHudson, J. I., Laird, N. M., & Betensky, R. A. (2001) · American Journal of Epidemiology · doi:10.1093/aje/153.5.500 · Cited by 47 · see citing works
Self-citationThe familial relationship between panic disorder and unipolar depression
Maier, W. (1995) · Journal of Psychiatric Research · doi:10.1016/0022-3956(95)00024-y · Cited by 46 · see citing works
Hudson, J. I., Laird, N. M., Betensky, R. A., Keck, P. E., & Pope, H. G. (2001) · American Journal of Epidemiology · doi:10.1093/aje/153.5.506 · Cited by 29 · see citing works
Self-citationExtracting Meaning from Comorbidity: Genetic Analyses That Make Sense
Simonoff, E. A. (2000) · Journal of Child Psychology and Psychiatry · doi:10.1111/1469-7610.00653 · Cited by 26 · see citing works
Regression methods for assessing familial aggregation of disease
Laird, N. M., & Cuenco, K. T. (2003) · Statistics in Medicine · doi:10.1002/sim.1504 · Cited by 15 · see citing works
Self-citationDirection of causation: Reply to commentaries
Neale, M. C., Duffy, D. L., & Martin, N. G. (1994) · Genetic Epidemiology · doi:10.1002/gepi.1370110603 · Cited by 12 · see citing works
Estimating the Prevalence of Disease Using Relatives of Case and Control ProbandsPreprint
Javaras, K. N., Laird, N. M., Hudson, J. I., & Ripley, B. D. (2007) · Collection of Biostatistics Research Archive · Cited by 2 · see citing works
Self-citation
Flagged first, then by citations
1 of the 36 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Endogenous Selection Bias: The Problem of Conditioning on a Collider Variable
Elwert, F., & Winship, C. (2014) · Annual Review of Sociology · doi:10.1146/annurev-soc-071913-043455 · Cited by 1,168 · see citing works
Hudson, J. I., Lalonde, J. K., Coit, C. E., Tsuang, M. T., McElroy, S. L., Crow, S. J., Bulik, C. M., Hudson, M., Yanovski, J. A., Rosenthal, N. R., et al. (2010) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2010.29203 · Cited by 296 · see citing works
Self-citationPrevalence and correlates of eating disorders in 875 patients with bipolar disorder
McElroy, S. L., Frye, M. A., Hellemann, G., Altshuler, L., Leverich, G. S., Suppes, T., Keck, P. E., Nolen, W. A., Kupka, R., & Post, R. M. (2011) · Journal of Affective Disorders · doi:10.1016/j.jad.2010.06.037 · Cited by 162 · see citing works
Family Study of Borderline Personality Disorder and Its Sectors of Psychopathology
Gunderson, J. G., Zanarini, M. C., Choi-Kain, L. W., Mitchell, K. S., Jang, K. L., & Hudson, J. I. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.65 · Cited by 110 · see citing works
Self-citationRietz, E. D., Brikell, I., Butwicka, A., Leone, M., Chang, Z., Cortese, S., D'Onofrio, B. M., Hartman, C. A., Lichtenstein, P., Faraone, S. V., et al. (2021) · The Lancet Psychiatry · doi:10.1016/s2215-0366(21)00171-1 · Cited by 110 · see citing works
Epidemiology of Eating Disorders
Wade, T. D., Keski‐Rahkonen, A., & Hudson, J. I. (2011) · Wiley eBooks · doi:10.1002/9780470976739.ch20 · Cited by 100 · see citing works
Self-citationBrikell, I., Ghirardi, L., D’Onofrio, B. M., Dunn, D. W., Almqvist, C., Dalsgaard, S., Kuja-Halkola, R., & Larsson, H. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.08.006 · Cited by 85 · see citing works
Clinical phenotype of bipolar disorder with comorbid binge eating disorder
McElroy, S. L., Crow, S. J., Biernacka, J. M., Winham, S. J., Geske, J. R., Barboza, A. B. C., Prieto, M. L., Chauhan, M., Seymour, L. R., Mori, N. N., et al. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2013.05.024 · Cited by 68 · see citing works
MINIMAL SUFFICIENT CAUSATION AND DIRECTED ACYCLIC GRAPHSPreprint
VanderWeele, T. J., & Robins, J. M. (2009) · Cited by 51 · see citing works
Self-citationMinimal sufficient causation and directed acyclic graphs
VanderWeele, T. J., & Robins, J. M. (2009) · The Annals of Statistics · doi:10.1214/08-aos613 · Cited by 52 · see citing works
Self-citationDiemer, E. W., Hudson, J. I., & Javaras, K. N. (2021) · Psychotherapy and Psychosomatics · doi:10.1159/000517104 · Cited by 51 · see citing works
Self-citationThe formal approach to quantitative causal inference in epidemiology: misguided or misrepresented?
Daniel, R., Stavola, B. L. D., & Vansteelandt, S. (2016) · International Journal of Epidemiology · doi:10.1093/ije/dyw227 · Cited by 59 · see citing works
Kanayama, G., Pope, H. G., & Hudson, J. I. (2018) · Psychological Medicine · doi:10.1017/s0033291718000508 · Cited by 42 · see citing works
Self-citationBipolar disorder with comorbid binge eating history: A genome-wide association study implicates APOB
Winham, S. J., Barboza, A. B. C., McElroy, S. L., Oliveros, A., Crow, S. J., Colby, C. L., Choi, D., Chauhan, M., Frye, M. A., & Biernacka, J. M. (2014) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.04.026 · Cited by 40 · see citing works
Chen, Q., Kuja-Halkola, R., Sjölander, A., Serlachius, E., Cortese, S., Faraone, S., Almqvist, C., & Larsson, H. (2017) · Journal of Child Psychology and Psychiatry and Allied Disciplines · doi:10.1111/jcpp.12686 · Cited by 39 · see citing works
Liu, S., Leone, M., Ludvigsson, J. F., Lichtenstein, P., Guðbjörnsdóttir, S., Landén, M., Bergen, S. E., Taylor, M. J., Larsson, H., Kuja‐Halkola, R., et al. (2022) · Diabetes Care · doi:10.2337/dc22-1053 · Cited by 32 · see citing works
Familial Coaggregation of Asthma and Type 1 Diabetes in Children
Smew, A. I., Lundholm, C., Savendahl, L. S., Lichtenstein, P., & Almqvist, C. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.0834 · Cited by 31 · see citing works
Parental disorders, childhood abuse, and binge eating in a large community sample
Sachs‐Ericsson, N., Keel, P. K., Holland, L. A., Selby, E. A., Verona, E., Cougle, J. R., & Palmer, E. (2011) · International Journal of Eating Disorders · doi:10.1002/eat.20938 · Cited by 28 · see citing works
Paternal age at childbirth and eating disorders in offspring
Javaras, K. N., Rickert, M. E., Thornton, L. M., Peat, C. M., Baker, J. H., Birgegård, A., Norring, C. E. A., Landén, M., Almqvist, C., Larsson, H., et al. (2016) · Psychological Medicine · doi:10.1017/s0033291716002610 · Cited by 27 · see citing works
Self-citationSidorchuk, A., Kuja‐Halkola, R., Runeson, B., Lichtenstein, P., Larsson, H., Rück, C., D'Onofrio, B. M., Mataix‐Cols, D., & de la Cruz, L. F. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0417-1 · Cited by 26 · see citing works
Classifying Adults with Binge Eating Disorder Based on Severity Levels
Dakanalis, A., Riva, G., Serino, S., Colmegna, F., & Clerici, M. (2017) · European Eating Disorders Review · doi:10.1002/erv.2518 · Cited by 24 · see citing works
Liu, S., Leone, M., Ludvigsson, J. F., Lichtenstein, P., D'Onofrio, B. M., Svensson, A., Guðbjörnsdóttir, S., Bergen, S. E., Larsson, H., Kuja‐Halkola, R., et al. (2022) · Diabetes Care · doi:10.2337/dc21-1347 · Cited by 22 · see citing works
Hudson, J. I., Zanarini, M. C., Mitchell, K. S., Choi-Kain, L. W., & Gunderson, J. G. (2014) · Psychological Medicine · doi:10.1017/s0033291713003140 · Cited by 18 · see citing works
Self-citationBirth weight and cognition in children with epilepsy
Jackson, D. C., Lin, J. J., Chambers, K. L., Kessler-Jones, A. M., Jones, J. E., Hsu, D., Stafstrom, C. E., Seidenberg, M., & Hermann, B. P. (2014) · Epilepsia · doi:10.1111/epi.12622 · Cited by 12 · see citing works
Familial autoimmunity in patients with idiopathic inflammatory myopathies
Che, W. I., Westerlind, H., Lundberg, I. E., Hellgren, K. E., Kuja‐Halkola, R., & Holmqvist, M. E. (2022) · Journal of Internal Medicine · doi:10.1111/joim.13573 · Cited by 10 · see citing works
Borderline Personality and Mood Disorders
Gunderson, J. G., & Choi-Kain, L. W. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1314-5 · Cited by 11 · see citing works
Feldman, A. L., Johansson, A. L. V., Lambert, P. C., Sieurin, J., Yang, F., Pedersen, N. L., & Wirdefeldt, K. (2013) · Neuroepidemiology · doi:10.1159/000355452 · Cited by 9 · see citing works
Obeïd, S., Chok, A., Sacre, H., Haddad, C., Tahan, F. E., Ghanem, L., Azar, J., & Hallit, S. R. (2020) · Perspectives In Psychiatric Care · doi:10.1111/ppc.12567 · Cited by 8 · see citing works
The nature of the association between binge-eating severity and metabolic syndrome
Dakanalis, A., & Clerici, M. (2017) · Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity · doi:10.1007/s40519-017-0386-9 · Cited by 8 · see citing works
Chen, C., Cheng, C., Chen, P., Wu, C., Lin, M., Su, M., Chang, C. Y., Pan, Y., Huang, Y., Fan, C.-C., et al. (2024) · European Journal of Epidemiology · doi:10.1007/s10654-024-01166-w · Cited by 7 · see citing works
Liu, Q., Jiang, Y., Frisell, T., Stridh, P., Shchetynsky, K., Alfredsson, L. S., Kockum, I. S., Manouchehrinia, A., & Jiang, X. (2024) · Journal of Autoimmunity · doi:10.1016/j.jaut.2024.103294 · Cited by 6 · see citing works
Che, W. I., Baecklund, F., Hellgren, K. E., Kuja‐Halkola, R., Lundberg, I. E., Westerlind, H., & Holmqvist, M. E. (2023) · Arthritis & Rheumatology · doi:10.1002/art.42493 · Cited by 4 · see citing works
Clinical phenotype and genetic risk factors for bipolar disorder with binge eating: an update
Barboza, A. B. C., Winham, S. J., Biernacka, J. M., Frye, M. A., & McElroy, S. L. (2019) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2019.1638764 · Cited by 4 · see citing works
Conclusion: Integration and Synthesis
Choi-Kain, L. W., & Gunderson, J. G. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1314-5_14 · Cited by 3 · see citing works
A cautionary note on the recently proposed ICE Falcon method
Sjölander, A., & Frisell, T. (2024) · International Journal of Epidemiology · doi:10.1093/ije/dyae131 · Cited by 2 · see citing works
Brikell, I. (2018) · Figshare · Cited by 2 · see citing works
What can genetically informative designs add to the understanding of ADHD
Chen, Q. (2016) · Figshare · Cited by 1 · see citing works
Yang, W., Komulainen, K., Niemi, R., Gutvilig, M., Böckerman, P., Elovainio, M. J., & Hakulinen, C. A. (2025) · Social Psychiatry and Psychiatric Epidemiology · doi:10.1007/s00127-025-02997-y
Smew, A. I., Gong, T., Kuja‐Halkola, R., Lundholm, C., Harder, A., Lu, Y., Savendahl, L. S., Lichtenstein, P., Brew, B. K., & Almqvist, C. (2025) · Journal of Allergy and Clinical Immunology Global · doi:10.1016/j.jacig.2025.100519
Familial Co‐Aggregation of Neurodevelopmental Conditions and Childhood‐Onset Type 1 Diabetes
Liu, S., Machado, G. M., Hardiansyah, I., Gu, X., Ludvigsson, J. F., Lichtenstein, P., Guðbjörnsdóttir, S., Rietz, E. D., D'Onofrio, B. M., Larsson, H., et al. (2026) · Acta Paediatrica · doi:10.1111/apa.70732
Khemiri, L., Kuja‐Halkola, R., Larsson, H., Brikell, I., Chang, Z., D'Onofrio, B. M., Latvala, A., & Lichtenstein, P. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03866-z
- Authors
- Hudson, J. I., Javaras, K. N., Laird, N. M., VanderWeele, T. J., Pope, H. G., & Hernán, M. A.
- Affiliations
- Harvard University (US)
- University of Chicago (US)
- Corresponding author
- Hudson, James I.
- Venue
- Epidemiology
- Published
- 2008-05
- Volume
- 19
- Issue
- 3
- Pages
- 431-439
- ISSN
- 1044-3983 (ISSN-L)
- OpenAlex
- W2032755500
- Cited by
- 42
- References
- 36
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 3 · 2014: 6 · 2013: 2
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centers for Disease Control and Prevention (5 T32 MN17119-22)
- National Institute of Mental Health (R01MH070377)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Keywords
- directed acyclic graphs, structural equation modeling, case-control sampling, causal effect estimation, binge eating disorder, bipolar disorder, genetic factors, family studies
- MeSH terms
- Bipolar Disorder, Bulimia, Family, Humans, Models, Genetic, Research Design, Comorbidity, Case-Control Studies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
