Hamilton
Anxiety Disorder Linkage & Association
ADAA 12th Annual Scientific Research Symposium
Genetic Linkage and Association Studies
of Anxiety Disorders
Steven P. Hamilton
GENERAL
A. The lifetime incidence of DSM-IV anxiety disorders is estimated to be 28.8%
among 9,282 participants in the National Comorbidity Survey Replication
(Kessler et al., 2005).
B. Females show a 1.6-fold higher risk for an anxiety disorder than do males.
C. Average age of onset of anxiety disorders was eleven years of age.
D. Lifetime prevalence:
a. 4.7% for panic disorder
b. 12.5% for specific phobia
c. 12.1% for social anxiety disorder
d. 5.7% for generalized anxiety disorder
e. 1.6% for obsessive-compulsive disorder
PANIC DISORDER
A. Early linkage studies (Crowe et al., 1987; 1990; Crowe et al., 2001).
B. More recent linkage studies (Knowles et al., 1998; Fyer et al., 2006; Gelernter et
al., 2001; Thorgeirsson et al., 2003).
C. Candidate genes:
a. ADORA2A (Deckert et al., 1998; Hamilton et al., 2004; Yamada et al.,
2001; Lam et al., 2005).
b. COMT (Hamilton et al., 2002; Woo et al., 2002; 2004; Domschke et al.,
2004; Rothe et al., 2006)
PHOBIAS
A.
Linkage studies (Gelernter et al., 2003; 2004)
B.
Extended phenotypes (Kaabi et al., 2006; Thorgeirsson et al., 2003; Hettema
et al., 2006).
C.
Social phobia candidate gene studies (Stein et al., 1998; Kennedy et al.,
2001).
GENERALIZED ANXIETY DISORDER
A. Linkage studies: none
B. Candidate gene studies (Tadic et al., 2003; Samochowiec et al., 2004).
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Hamilton
Anxiety Disorder Linkage & Association
OBSESSIVE-COMPULSIVE DISORDER
A.
Linkage studies (Hanna et al., 2002; Hanna et al., 2007; Willour et al., 2004;
Shugart et al., 2006; Samuels et al., 2007)
B.
Candidate gene studies
a. SLC6A4 (Altemus et al., 1996; Di Bella et al., 1996; Ozaki et al., 2003; Hu
et al., 2006; Wendland et al., 2007; Dickel et al., 2007; Lin, 2007)
b. COMT (Karayiorgou et al., 1997; Karayiorgou et al., 1999; Azzam and
Mathews, 2003; Denys et al., 2006; Pooley et al., 2007).
c. Other genes (Hemmings and Stein, 2006; Veenstra-VanderWeele et al.,
2001; Arnold et al., 2006; Dickel et al., 2006).
ANXIOUS PERSONALITY TRAITS
A. Linkage studies (Fullerton et al., 2003; Nash et al., 2004; Neale et al., 2005)
B. GWAS (Shifman et al., 2007; van den Oord et al., 2008).
C. Candidate genes (Lesch et al., 1996; Willis-Owen et al., 2005; Middeldorp et al.,
2007).
ANIMAL STUDIES OF ANXIETY
A. QTLs (Flint et al., 2005; 1995; Turri et al., 1999; 2001a; 2001b; 2004;
Gershenfeld and Paul, 1997; Gershenfeld et al., 1997; Willis-Owen and Flint,
2006; Wehner et al., 1997; Caldarone et al., 1997; Fernandez-Teruel et al., 2002)
B. Gene targeting studies
C.
HTR1A (Heisler et al., 1998; Ramboz et al., 1998; Parks et al.,
1998; Ramboz et al., 1998; Gross et al., 2002; Kusserow et al.,
2004; Santarelli et al., 2003; Klemenhagen et al., 2005)
D.
CRH (Weninger et al., 1999; Smith et al., 1998; Timpl et al., 1998;
Kishimoto et al., 2000; Bale et al., 2000; Coste et al., 2000)
CONCLUSION
A. GWAS
B. CNVs/Epigenetics
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Anxiety Disorder Linkage & Association
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Anxiety Disorder Linkage & Association
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Anxiety Disorder Linkage & Association
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170R: Friday 3/13, 8:00am, WolfABC
th
Presented at the ADAA 29 Annual Conference