ADD/ADHD Research

A genomewide scan for attention-deficit/hyperactivity disorder in an extended sample: suggestive linkage on 17p11

Matthew N. Ogdie,1 I. Laurence Macphie,5 Sonia L. Minassian,3,4 May Yang,4 Simon E. Fisher,5 Clyde Francks,5 Rita M. Cantor,1 James T. McCracken,2 James J. McGough,2 Stanley F. Nelson,1,4,* Anthony P. Monaco,5,* and Susan L. Smalley2,4,* Departments of 1Human Genetics, 2Psychiatry and Biobehavioral Sciences, and 3Biostatistics, and 4Center for Neurobehavioral Genetics, University of California, Los Angeles, Los Angeles; and 5Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom

The Wellcome Trust Centre for Human Genetics (WTCHG) was established in 1994 to undertake research into the genetic basis of common diseases. Since June 2000 the Centre has been located in the Henry Wellcome Building of Genomic Medicine, University of Oxford.

The scientific objective of the Centre is to explore all aspects of the genetic susceptibility of disease including the localisation of genes involved in common diseases, characterisation of the variants responsible for susceptibility, the understanding of how these DNA variants may contribute to risk of disease in the population and finally, how such genetic factors contribute biologically to a disease process.

The Centre houses multi-disciplinary research teams in human genetics, functional genomics, bioinformatics, statistical genetics and structural biology.

A genomewide scan for attention-deficit/hyperactivity disorder in an extended sample: suggestive linkage on 17p11

Matthew N. Ogdie,1 I. Laurence Macphie,5 Sonia L. Minassian,3,4 May Yang,4 Simon E. Fisher,5 Clyde Francks,5 Rita M. Cantor,1 James T. McCracken,2 James J. McGough,2 Stanley F. Nelson,1,4,* Anthony P. Monaco,5,* and Susan L. Smalley2,4,*
Departments of 1Human Genetics, 2Psychiatry and Biobehavioral Sciences, and 3Biostatistics, and 4Center for Neurobehavioral Genetics, University of California, Los Angeles, Los Angeles; and 5Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom

Attention-deficit/hyperactivity disorder (ADHD [MIM 143465]) is a common, highly heritable neurobehavioral disorder of childhood onset, characterized by hyperactivity, impulsivity, and/or inattention. As part of an ongoing study of the genetic etiology of ADHD, we have performed a genomewide linkage scan in 204 nuclear families comprising 853 individuals and 270 affected sibling pairs (ASPs). Previously, we reported genomewide linkage analysis of a "first wave" of these families composed of 126 ASPs. A follow-up investigation of one region on 16p yielded significant linkage in an extended sample. The current study extends the original sample of 126 ASPs to 270 ASPs and provides linkage analyses of the entire sample, using polymorphic microsatellite markers that define an approximately 10-cM map across the genome. Maximum LOD score (MLS) analysis identified suggestive linkage for 17p11 (MLS=2.98) and four nominal regions with MLS values >1.0, including 5p13, 6q14, 11q25, and 20q13. These data, taken together with the fine mapping on 16p13, suggest two regions as highly likely to harbor risk genes for ADHD: 16p13 and 17p11. Interestingly, both regions, as well as 5p13, have been highlighted in genomewide scans for autism.

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