Attention deficit hyperactivity disorder: fine mapping supports linkage to 5p13, 6q12, 16p13, and 17p11.
We completed fine mapping of nine positional candidate regions for attention-deficit/hyperactivity disorder (ADHD) in an extended population sample of 308 affected sibling pairs (ASPs), constituting the largest linkage sample of families with ADHD published to date. The candidate chromosomal regions were selected from all three published genomewide scans for ADHD, and fine mapping was done to comprehensively validate these positional candidate regions in our sample. Multipoint maximum LOD score (MLS) analysis yielded significant evidence of linkage on 6q12 (MLS 3.30; empiric P=.024) and 17p11 (MLS 3.63; empiric P=.015), as well as suggestive evidence on 5p13 (MLS 2.55; empiric P=.091). In conjunction with the previously reported significant linkage on the basis of fine mapping 16p13 in the same sample as this report, the analyses presented here indicate that four chromosomal regions--5p13, 6q12, 16p13, and 17p11--are likely to harbor susceptibility genes for ADHD. The refinement of linkage within each of these regions lays the foundation for subsequent investigations using association methods to detect risk genes of moderate effect size.
Human Genetics, University of California-Los Angeles, Los Angeles, CA, USA.
Matthew N
MN
Ogdie
Simon E
SE
Fisher
May
M
Yang
Janeen
J
Ishii
Clyde
C
Francks
Sandra K
SK
Loo
Rita M
RM
Cantor
James T
JT
McCracken
James J
JJ
McGough
Susan L
SL
Smalley
Stanley F
SF
Nelson
D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008126:Lod Score; D035781:Siblings
D005819:Genetic Markers