A Genomewide Scan for Attention-Deficit/Hyperactivity Disorder in an Extended Sample: Suggestive Linkage on 17p11

Abstract

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.

Suggestive linkage of ADHD to chromosome 18q22 in a young genetically isolated Dutch population

“…However, subgroup analyses may cause false-positive findings and remain to be confirmed. When considering other regions that were suggested by others, the region 6q15 that had a HLOD of 1.13 in our study and also harbours serotonin receptor genes HTR1B and HTR1E is adjacent (distance ¼ 10 cM) to the region 6q14, which was identified by Ogdie et al 23,24 as a nominally significant susceptibility locus for ADHD. Our genome scan also showed some evidence of linkage to 5q33 (conservative homozygosity mapping HLOD 1.03, marker D5S422) (Figure 2c).…”

The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes

“…11 To date, there have been four published genome linkage scans of ADHD; three affected sibling pair studies and one of 16 multiplex pedigrees. [12][13][14][15][16][17][18] These studies have highlighted a number of potential linkage regions for further exploration, although there is as yet no clear consensus across the various data sets and no genes have been identified that account for linkage signals. Several of the linkage regions overlap in two or more of these studies, including regions of chromosomes 5p, 6q, 7p, 11q, 12q and 17p, suggesting that one or more loci of moderately large effect may exist.…”

Association of the dopamine receptor D4 (DRD4) gene 7‐repeat allele with children with attention‐deficit/hyperactivity disorder (ADHD): An update

“…Family, twin and adoption studies, as well as linkage and association studies, have shown strong genetic contributions to the etiology of ADHD [Faraone and Biederman, 1998;Fisher et al, 2002;Ogdie et al, 2003; ArcosBurgos et al, 2004]. The most consistently replicated candidate gene in ADHD genetics is the association with the dopamine receptor D4 gene (DRD4) [LaHoste et al, 1996;Smalley et al, 1998;Swanson et al, 1998;Comings et al, 1999;Faraone et al, 1999;Holmes et al, 2000;Muglia et al, 2000;Tahir et al, 2000;Curran et al, 2001;Mill et al, 2001;Roman et al, 2001;Bhaduri et al, 2006].…”