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Family‐based and case‐control association studies of catechol‐ O ‐methyltransferase in attention deficit hyperactivity disorder suggest genetic sexual dimorphism
Author(s) -
Qian Qiujin,
Wang Yufeng,
Zhou Rulun,
Li Jun,
Wang Bing,
Glatt Stephen,
Faraone Stephen V.
Publication year - 2002
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.10064
Subject(s) - attention deficit hyperactivity disorder , novelty seeking , proband , psychology , allele , catechol o methyl transferase , rs4680 , clinical psychology , population , psychiatry , personality , medicine , temperament , genetics , biology , gene , social psychology , environmental health , mutation
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.