Association of Attention-Deficit/Hyperactivity Disorder with a Candidate Region for Reading Disabilities on Chromosome 6p

被引:45
作者
Couto, Jillian M. [1 ]
Gomez, Lissette [1 ]
Wigg, Karen [1 ]
Ickowicz, Abel [3 ]
Pathare, Tejaswee [3 ]
Malone, Molly [3 ]
Kennedy, James L. [2 ]
Schachar, Russell [3 ]
Barr, Cathy L. [1 ,3 ]
机构
[1] Univ Hlth Network, Toronto Western Hosp, Toronto Western Res Inst, Genet & Dev Div, Toronto, ON M5T 2S8, Canada
[2] Univ Toronto, Dept Psychiat, Ctr Addict & Mental Hlth, Neurogenet Sect, Toronto, ON, Canada
[3] Hosp Sick Children, Program Neurosci & Mental Hlth, Toronto, ON M5G 1X8, Canada
关键词
ADHD; genetic association; pleiotropic locus; RD; DEFICIT HYPERACTIVITY DISORDER; QUANTITATIVE-TRAIT LOCUS; FAMILY-BASED TESTS; SUSCEPTIBILITY LOCUS; SPELLING DISABILITY; SUGGESTIVE EVIDENCE; COGNITIVE DEFICITS; LINKAGE; DYSLEXIA; GENE;
D O I
10.1016/j.biopsych.2009.02.016
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
Background: Reading disabilities (RD) and attention-deficit hyperactivity/disorder (ADHD) are two common childhood disorders that co-occur by chance more often than expected. Twin studies and overlapping genetic linkage findings indicate that shared genetic factors partially contribute to this comorbidity. Linkage of ADHD to 6p, an identified RD candidate locus, has previously been reported, suggesting the possibility of a pleiotropic gene at this locus. RD has been previously associated with five genes in the region, particularly DCDC2 and KIAA0319. Methods: To test whether these genes also contribute to ADHD, we investigated markers previously associated with RD for association with ADHD and ADHD symptoms in a sample of families with ADHD (n = 264). Markers were located in two subregions, VMP/DCDC2 and KIAA0319/TTRAP. Results: Across all analyses conducted, strong evidence for association was observed in the VMP/DCDC2 region. Association was equally strong with symptoms of both inattention and hyperactivity/impulsivity, suggesting that this locus contributes to both symptom dimensions. Markers were also tested for association with measures of reading skills (word identification, decoding); however, there was virtually no overlap in the markers associated with ADHD and those associated with reading skills in this sample. Conclusions: Overall this study supports a previous linkage study of ADHD indicating a risk gene for ADHD on 6p and points to VMP or DCDC2 as the most likely candidates.
引用
收藏
页码:368 / 375
页数:8
相关论文
共 72 条
[1]
Merlin-rapid analysis of dense genetic maps using sparse gene flow trees [J].
Abecasis, GR ;
Cherny, SS ;
Cookson, WO ;
Cardon, LR .
NATURE GENETICS, 2002, 30 (01) :97-101
[2]
A haplotype map of the human genome [J].
Altshuler, D ;
Brooks, LD ;
Chakravarti, A ;
Collins, FS ;
Daly, MJ ;
Donnelly, P ;
Gibbs, RA ;
Belmont, JW ;
Boudreau, A ;
Leal, SM ;
Hardenbol, P ;
Pasternak, S ;
Wheeler, DA ;
Willis, TD ;
Yu, FL ;
Yang, HM ;
Zeng, CQ ;
Gao, Y ;
Hu, HR ;
Hu, WT ;
Li, CH ;
Lin, W ;
Liu, SQ ;
Pan, H ;
Tang, XL ;
Wang, J ;
Wang, W ;
Yu, J ;
Zhang, B ;
Zhang, QR ;
Zhao, HB ;
Zhao, H ;
Zhou, J ;
Gabriel, SB ;
Barry, R ;
Blumenstiel, B ;
Camargo, A ;
Defelice, M ;
Faggart, M ;
Goyette, M ;
Gupta, S ;
Moore, J ;
Nguyen, H ;
Onofrio, RC ;
Parkin, M ;
Roy, J ;
Stahl, E ;
Winchester, E ;
Ziaugra, L ;
Shen, Y .
NATURE, 2005, 437 (7063) :1299-1320
[3]
[Anonymous], 1995, MANUAL CHILDRENS DEP
[4]
A whole-genome scan in 164 Dutch sib pairs with attention-deficit/hyperactivity disorder: Suggestive evidence for linkage on chromosomes 7p and 15q [J].
Bakker, SC ;
van der Meulen, EM ;
Buitelaar, JK ;
Sandkuijl, LA ;
Pauls, DL ;
Monsuur, AJ ;
van't Slot, R ;
Minderaa, RB ;
Gunning, WB ;
Pearson, PL ;
Sinke, RJ .
AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 72 (05) :1251-1260
[5]
Replication of reported linkages for dyslexia and spelling and suggestive evidence for novel regions on chromosomes 4 and 17 [J].
Bates, Timothy C. ;
Luciano, Michelle ;
Castles, Anne ;
Coltheart, Max ;
Wright, Margaret J. ;
Martin, Nicholas G. .
EUROPEAN JOURNAL OF HUMAN GENETICS, 2007, 15 (02) :194-203
[6]
EVALUATION OF THE REVISED ONTARIO CHILD HEALTH STUDY SCALES [J].
BOYLE, MH ;
OFFORD, DR ;
RACINE, Y ;
FLEMING, JE ;
SZATMARI, P ;
SANFORD, M .
JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, 1993, 34 (02) :189-213
[7]
QUANTITATIVE TRAIT LOCUS FOR READING-DISABILITY (VOL 266, PG 276, 1994) [J].
CARDON, LR ;
SMITH, SD ;
FULKER, DW ;
KIMBERLING, WJ ;
PENNINGTON, BF ;
DEFRIES, JC .
SCIENCE, 1995, 268 (5217) :1553-1553
[8]
QUANTITATIVE TRAIT LOCUS FOR READING-DISABILITY ON CHROMOSOME-6 [J].
CARDON, LR ;
SMITH, SD ;
FULKER, DW ;
KIMBERLING, WJ ;
PENNINGTON, BF ;
DEFRIES, JC .
SCIENCE, 1994, 266 (5183) :276-279
[9]
Transmission/disequilibrium tests for extended marker haplotypes [J].
Clayton, D ;
Jones, H .
AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 65 (04) :1161-1169
[10]
Conners CK., 1997, CONNERS RATING SCALE