Family‐based and case‐control association studies of catechol‐O‐methyltransferase in attention deficit hyperactivity disorder suggest genetic sexual dimorphism
Open accessAbstract
Attention deficit hyperactivity disorder (ADHD) is the most common childhood‐onset behavioral disorder. Boys are more often affected than girls. Family, twin, and adoption studies have supported a strong genetic basis. Some studies show that a catechol‐O‐methyltransferase (COMT) polymorphism affecting enzyme activity was associated with personality characteristics and diseases, such as novelty‐seeking personality, substance abuse, and heroin addiction, whose features are similar to ADHD or are associated with ADHD. These findings suggest that the COMT gene may be a candidate gene for ADHD. TDT, HHRR, and case‐control association studies were conducted within a sample of 202 nuclear ADHD families, 340 ADHD cases, and 226 controls in the Han Chinese population. Diagnoses and ADHD subtypes were ascertained according to DSM‐IV criteria using American Clinical Diagnostic Interviewing Scales. The HHRR analysis suggested that the low enzyme‐activity COMT Met allele was preferentially transmitted to ADHD boys (160 trios, χ 2 = 3.858, P = 0.05, df = 1) but not girls. This association is particularly pronounced among male ADHD probands without any comorbidity (50 trios, HHRR: χ 2 = 5.128, P = 0.024, df = 1; TDT: χ 2 = 4.558, P = 0.033, df = 1), especially the ADHD‐I subtype (32 trios, HHRR: χ 2 = 5.792, P = 0.016, df = 1; TDT: χ 2 = 5.333, P = 0.021, df = 1). The case‐control study revealed that the Val allele was more frequent in females meeting ICD‐10 or DSM‐IV criteria for ADHD than in female controls (86 and 79.5%, respectively, χ 2 = 4.059, P = 0.044, df = 1). Although these results suggest the COMT gene exerts some influence on the risk for ADHD in the Han Chinese population, given the potential for Type I error, these findings require replication before drawing definitive conclusions. © 2003 Wiley‐Liss, Inc.
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?
Some evidence suggests that gender could be a moderating factor with Met being the risk allele in boys.
“some evidence suggests that gender could be a moderating factor with Met being the risk allele in boys (Biederman et al, 2008; Qian et al, 2003)”
From DAT1 and COMT effects on delay discounting and trait impulsivity in male adolescents with attention deficit/hyperactivity disorder and healthy controls (2010) · cites this paper as Qian et al, 2003
Met is the risk allele in boys.
“Met being the risk allele in boys (Biederman et al, 2008; Qian et al, 2003).”
From DAT1 and COMT effects on delay discounting and trait impulsivity in male adolescents with attention deficit/hyperactivity disorder and healthy controls (2010) · cites this paper as Qian et al, 2003
Cites
Diagnostic and Statistical Manual of Mental Disorders
(2012) · Springer eBooks · doi:10.1007/springerreference_121117 · Cited by 20,769 · see citing works
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition
(2013) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9780890425596.893619 · Cited by 4,390 · see citing works
Spielman, R. S., McGinnis, R. E., & Ewens, W. J. (1993) · PubMed · Cited by 3,679 · see citing works
Effect of COMT Val 108/158 Met genotype on frontal lobe function and risk for schizophrenia
Egan, M. F., Goldberg, T. E., Kolachana, B. S., Callicott, J. H., Mazzanti, C. M., Straub, R. E., Goldman, D. A., & Weinberger, D. R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111134598 · Cited by 2,374 · see citing works
Lotta, T. I., Vidgren, J., Tilgmann, C., Ulmanen, I., Melén, K., Julkunen, I., & Taskinen, J. (1995) · Biochemistry · doi:10.1021/bi00013a008 · Cited by 1,167 · see citing works
Attention-deficit hyperactivity disorder : a clinical workbook
Barkley, R. A., & Murphy, K. R. (1991) · Cited by 1,144 · see citing works
Cohen, P., Cohen, J., Kasen, S., Velez, C. N., Hartmark, C., Johnson, J., Rojas, M., Brook, J., & Streuning, E. L. (1993) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.1993.tb01094.x · Cited by 957 · see citing works
The TDT and other family-based tests for linkage disequilibrium and association.
(1996) · PubMed Central · Cited by 901 · see citing works
Gogos, J. A., Morgan, M., Luine, V., Santha, M., Ogawa, S., Pfaff, D., & Karayiorgou, M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.17.9991 · Cited by 864 · see citing works
Neurobiology of attention-deficit hyperactivity disorder
Faraone, S. V., & Biederman, J. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00240-6 · Cited by 811 · see citing works
Self-citationBiederman, J. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820090056010 · Cited by 771 · see citing works
Late‐Onset psychosis in the velo‐cardio‐facial syndrome
Shprintzen, R. J., Goldberg, R. B., Golding‐Kushner, K. J., & Marion, R. W. (1992) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320420131 · Cited by 402 · see citing works
Global variation in the frequencies of functionally different catechol-O-methyltransferase alleles.
Palmatier, M., Kang, M. A., & Kidd, K. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00098-0 · Cited by 385 · see citing works
Sex differences in dopamine receptors and their relevance to ADHD
Andersen, S. L., & Teicher, M. H. (2000) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(99)00044-5 · Cited by 353 · see citing works
The Nature and Heritability of Attention-Deficit/Hyperactivity Disorder
Faraone, S. V., & Doyle, A. E. (2001) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/s1056-4993(18)30059-2 · Cited by 304 · see citing works
Self-citationKarayiorgou, M., Altemus, M., Galke, B. L., Goldman, D., Murphy, D. L., Ott, J., & Gogos, J. A. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4572 · Cited by 304 · see citing works
Chromosomal mapping of the human catechol-O-methyltransferase gene to 22q11.1→q11.2
Grossman, M. H., Emanuel, B. S., & Budarf, M. L. (1992) · Genomics · doi:10.1016/0888-7543(92)90316-k · Cited by 296 · see citing works
Karayiorgou, M., Sobin, C. A., Blundell, M. L., Galke, B. L., Malinova, L., Goldberg, P. H., Ott, J., & Gogos, J. A. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00319-9 · Cited by 263 · see citing works
Molecular definition of the 22q11 deletions in velo-cardio-facial syndrome.
Morrow, B. E., Goldberg, R. B., Carlson, C., et al. (1995) · PubMed · Cited by 245 · see citing works
Benjamin, J., Osher, Y., Kotler, M., Gritsenko, I., Nemanov, L., Belmaker, R. H., & Ebstein, R. P. (2000) · Molecular Psychiatry · doi:10.1038/sj.mp.4000640 · Cited by 196 · see citing works
Reduced Brain Metabolism in Hyperactive Girls
Monique Ernst, D., Liebenauer, L. L., King, A. C., FITZGERALD, G. A., Cohen, R. M., & Zametkin, A. J. (1994) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199407000-00012 · Cited by 192 · see citing works
Scanlon, P. D., Raymond, F. A., & Weinshilboum, R. M. (1979) · Science · doi:10.1126/science.758679 · Cited by 153 · see citing works
Preferential transmission of the high activity allele of COMT in schizophrenia
Li, T., Sham, P. C., Vallada, H., Xie, T., Tang, X., Murray, R. M., Liu, X., & Collier, D. A. (1996) · Psychiatric Genetics · doi:10.1097/00041444-199623000-00005 · Cited by 127 · see citing works
A family study of patients with attention deficit disorder and normal controls
Biederman, J., Münir, K., Knee, D., Habelow, W., Armentano, M. E., Autor, S., Hoge, S. K., & WATERNAUX, C. M. (1986) · Journal of Psychiatric Research · doi:10.1016/0022-3956(86)90030-0 · Cited by 125 · see citing works
Milberger, S., Biederman, J., Faraone, S., Chen, L., & Jones, J. (1997) · American Journal on Addictions · doi:10.3109/10550499709136987 · Cited by 115 · see citing works
Self-citationSuicidal behavior in patients with schizophrenia is related to COMT polymorphism
Nolan, K. A., Volavka, J., Czobor, P., Cseh, A., Lachman, H. M., Saito, T., Tiihonen, J., Putkonen, A., Hallikainen, T., Kotilainen, I., et al. (2000) · Psychiatric Genetics · doi:10.1097/00041444-200010030-00003 · Cited by 114 · see citing works
Linkage of a composite inhibitory phenotype to a chromosome 22q locus in eight Utah families
Myles‐Worsley, M., Coon, H. H., McDowell, J. E., Brenner, C. A., Hoff, M., Lind, B., Bennett, P., Freedman, R., Clementz, B. A., & Byerley, W. (1999) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19991015)88:5 · Cited by 98 · see citing works
An exploratory study of ADHD among second-degree relatives of ADHD children
Faraone, S. V., Biederman, J., & Milberger, S. (1994) · Biological Psychiatry · doi:10.1016/0006-3223(94)90006-x · Cited by 85 · see citing works
Self-citationRelationship of sleep abnormalities to patient genotypes in Prader-Willi syndrome
Vgontzas, A. N., Kales, A., Seip, J. R., Mascari, M. J., Bixler, E. O., Myers, D. C., Vela‐Bueno, A., & Rogan, P. K. (1996) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19960920)67:5 · Cited by 73 · see citing works
Ovtscharoff, W. A., Eusterschulte, B., Zienecker, R., Reisert, I., & Pilgrim, C. (1992) · The Journal of Comparative Neurology · doi:10.1002/cne.903230212 · Cited by 61 · see citing works
Weinshilboum, R. M., & Dunnette, J. H. (1981) · Clinical Genetics · doi:10.1111/j.1399-0004.1981.tb00740.x · Cited by 46 · see citing works
Arolt, V., Lencer, R., Purmann, S., Sch�rmann, M., M�ller-Myhsok, B., Krecker, K., & SCHWINGER, E. (1999) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19991215)88:6 · Cited by 46 · see citing works
Milberger, S., Biederman, J., Faraone, S. V., Chen, L., & Jones, J. T. (1997) · American Journal on Addictions · doi:10.1111/j.1521-0391.1997.tb00399.x · Cited by 43 · see citing works
Self-citationChen, C.-H., Lee, Y.-R., Wei, F., Koong, F., Hwu, H., & Hsiao, K. (1997) · Biological Psychiatry · doi:10.1016/s0006-3223(97)00045-0 · Cited by 36 · see citing works
Donnelly, S. L., Wolpert, C. M., Menold, M. M., Bass, M. P., Gilbert, J. R., Cuccaro, M. L., Delong, G. R., & Pericak-Vance, M. A. (2000) · American Journal of Medical Genetics · doi:10.1002/1096-8628(20000612)96:3
Young (2000) · doi:10.1002/1096-8628(20001009)96:5
Jonnal (2000) · doi:10.1002/1096-8628(20001204)96:6
Flagged first, then by citations
Cited by
Sorted by citations
Molecular genetics of attention-deficit/hyperactivity disorder
Faraone, S. V., Perlis, R. H., Doyle, A. E., Smoller, J. W., Goralnick, J. J., Holmgren, M. A., & Sklar, P. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.11.024 · Cited by 2,357 · see citing works
Self-citationsagvolden, T., johansen, E. B., aase, H., & russell, V. A. (2005) · Behavioral and Brain Sciences · doi:10.1017/s0140525x05000075 · Cited by 1,035 · see citing works
Candidate gene studies of ADHD: a meta-analytic review
Gizer, I. R., Ficks, C., & Waldman, I. D. (2009) · Human Genetics · doi:10.1007/s00439-009-0694-x · Cited by 1,020 · see citing works
Bilder, R. M., Volavka, J., Lachman, H. M., & Grace, A. A. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300542 · Cited by 769 · see citing works
Brookes, K., Xu, X., Chen, W., Zhou, K., Neale, B., Lowe, N., Aneey, R., Franke, B., Gill, M., Ebstein, R., et al. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001869 · Cited by 533 · see citing works
Self-citationHypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder
Abdolmaleky, H. M., Cheng, K.-H., Faraone, S. V., Wilcox, M., Glatt, S. J., Gao, F., Smith, C. L., Shafa, R., Aeali, B., Carnevale, J., et al. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl253 · Cited by 462 · see citing works
Self-citationCraddock, N., Owen, M. J., & O'Donovan, M. C. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001808 · Cited by 216 · see citing works
Paloyelis, Y., Asherson, P., Mehta, M. A., Faraone, S. V., & Kuntsi, J. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.124 · Cited by 180 · see citing works
Self-citationNohesara, S., Ghadirivasfi, M., Mostafavi, S., Eskandari, M.-R., Ahmadkhaniha, H., Thiagalingam, S., & Abdolmaleky, H. M. (2011) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2011.06.013 · Cited by 168 · see citing works
Biederman, J., Kim, J. W., Doyle, A. E., Mick, E., Fagerness, J., Smoller, J. W., & Faraone, S. V. (2008) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30874 · Cited by 100 · see citing works
Self-citationChen, C., Chen, C., Moyzis, R., Stern, H., He, Q., Li, H., Li, J., Zhu, B., & Dong, Q. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021636 · Cited by 95 · see citing works
Self-citationReview: Genetics of Attention Deficit/Hyperactivity Disorder
Wallis, D., Russell, H. F., & Muenke, M. (2008) · Journal of Pediatric Psychology · doi:10.1093/jpepsy/jsn049 · Cited by 86 · see citing works
Effects of sex and COMT genotype on environmentally modulated cognitive control in mice
Papaleo, F., Erickson, L., Liu, G., Chen, J., & Weinberger, D. R. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1214397109 · Cited by 81 · see citing works
Eisenlohr-Moul, T. A., DeWall, C. N., Girdler, S. S., & Segerstrom, S. C. (2015) · Biological Psychology · doi:10.1016/j.biopsycho.2015.03.016 · Cited by 57 · see citing works
Michaelovsky, E., Gothelf, D., Korostishevsky, M., Frisch, A., Burg, M., Carmel, M., Steinberg, T., Inbar, D., Apter, A., & Weizman, A. (2008) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145707008085 · Cited by 53 · see citing works
Pálmason, H., Moser, D., Sigmund, J., Vogler, C., Hänig, S., Schneider, A., Seitz, C., Marcus, A., Meyer, J., & Freitag, C. M. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-009-0338-2 · Cited by 44 · see citing works
Chen, C., Liu, C., Chen, C., Moyzis, R., Chen, W., & Dong, Q. (2015) · Physiology & Behavior · doi:10.1016/j.physbeh.2014.09.005 · Cited by 7 · see citing works
- Authors
- Qian, Q., Wang, Y., Zhou, R., Li, J., Wang, B., Glatt, S., & Faraone, S. V.
- Affiliations
- Peking University (CN)
- Harvard University (US)
- Corresponding author
- Wang, Yufeng
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2002-12-16
- Volume
- 118B
- Issue
- 1
- Pages
- 103-109
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- OpenAlex
- W1981998761
- Cited by
- 113
- References
- 38
- Citations by year
- 2023: 2 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 7 · 2014: 5 · 2013: 11 · 2012: 6
- FWCI
- 5.14
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- SUNY Digital Repository Support (State University of New York System) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute of Mental Health (R25 MH60485, R25MH060485)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- attention deficit hyperactivity disorder, catechol-O-methyltransferase, COMT gene, candidate genes, Han Chinese, ADHD subtypes, transmission disequilibrium test, ADHD comorbidity, family-based association
- MeSH terms
- Adolescent, Adult, Alleles, Attention Deficit Disorder with Hyperactivity, Catechol O-Methyltransferase, Child, DNA, Family Health, Female, Gene Frequency, Genotype, Haplotypes, Humans, Male, Methionine, Nuclear Family, Phenotype, Polymorphism, Genetic, Sex Factors, Valine, Linkage Disequilibrium, Chi-Square Distribution, Case-Control Studies, Mutation, Missense
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
