Sapap3 and pathological grooming in humans: Results from the OCD collaborative genetics study.
SAP90/PSD95-associated protein (SAPAP) family proteins are post-synaptic density (PSD) components that interact with other proteins to form a key scaffolding complex at excitatory (glutamatergic) synapses. A recent study found that mice with a deletion of the Sapap3 gene groomed themselves excessively, exhibited increased anxiety-like behaviors, and had cortico-striatal synaptic defects, all of which were preventable with lentiviral-mediated expression of Sapap3 in the striatum; the behavioral abnormalities were also reversible with fluoxetine. In the current study, we sought to determine whether variation within the human Sapap3 gene was associated with grooming disorders (GDs: pathologic nail biting, pathologic skin picking, and/or trichotillomania) and/or obsessive-compulsive disorder (OCD) in 383 families thoroughly phenotyped for OCD genetic studies. We conducted family-based association analyses using the FBAT and GenAssoc statistical packages. Thirty-two percent of the 1,618 participants met criteria for a GD, and 65% met criteria for OCD. Four of six SNPs were nominally associated (P < 0.05) with at least one GD (genotypic relative risks: 1.6-3.3), and all three haplotypes were nominally associated with at least one GD (permuted P < 0.05). None of the SNPs or haplotypes were significantly associated with OCD itself. We conclude that Sapap3 is a promising functional candidate gene for human GDs, though further work is necessary to confirm this preliminary evidence of association.
Bienvenu
O J
OJ
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. jbienven@jhmi.edu
Wang
Y
Y
Shugart
Y Y
YY
Welch
J M
JM
Grados
M A
MA
Fyer
A J
AJ
Rauch
S L
SL
McCracken
J T
JT
Rasmussen
S A
SA
Murphy
D L
DL
Cullen
B
B
Valle
D
D
Hoehn-Saric
R
R
Greenberg
B D
BD
Pinto
A
A
Knowles
J A
JA
Piacentini
J
J
Pauls
D L
DL
Liang
K Y
KY
Willour
V L
VL
Riddle
M
M
Samuels
J F
JF
Feng
G
G
Nestadt
G
G
D000293:Adolescent; D002648:Child; D003299:Cooperative Behavior; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D006920:Hygiene; D015810:Linkage Disequilibrium; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009771:Obsessive-Compulsive Disorder / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000074407:SAP90-PSD95 Associated Proteins
C543515:DLGAP3 protein, human; D009419:Nerve Tissue Proteins; D000074407:SAP90-PSD95 Associated Proteins