Association study of 182 candidate genes in anorexia nervosa.
We performed association studies with 5,151 SNPs that were judged as likely candidate genetic variations conferring susceptibility to anorexia nervosa (AN) based on location under reported linkage peaks, previous results in the literature (182 candidate genes), brain expression, biological plausibility, and estrogen responsivity. We employed a case-control design that tested each SNP individually as well as haplotypes derived from these SNPs in 1,085 case individuals with AN diagnoses and 677 control individuals. We also performed separate association analyses using three increasingly restrictive case definitions for AN: all individuals with any subtype of AN (All AN: n = 1,085); individuals with AN with no binge eating behavior (AN with No Binge Eating: n = 687); and individuals with the restricting subtype of AN (Restricting AN: n = 421). After accounting for multiple comparisons, there were no statistically significant associations for any individual SNP or haplotype block with any definition of illness. These results underscore the importance of large samples to yield appropriate power to detect genotypic differences in individuals with AN and also motivate complementary approaches involving Genome-Wide Association (GWA) studies, Copy Number Variation (CNV) analyses, sequencing-based rare variant discovery assays, and pathway-based analysis in order to make up for deficiencies in traditional candidate gene approaches to AN.
Pinheiro
Andrea Poyastro
AP
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7160, USA.
Bulik
Cynthia M
CM
Thornton
Laura M
LM
Sullivan
Patrick F
PF
Root
Tammy L
TL
Bloss
Cinnamon S
CS
Berrettini
Wade H
WH
Schork
Nicholas J
NJ
Kaye
Walter H
WH
Bergen
Andrew W
AW
Magistretti
Pierre
P
Brandt
Harry
H
Crawford
Steve
S
Crow
Scott
S
Fichter
Manfred M
MM
Goldman
David
D
Halmi
Katherine A
KA
Johnson
Craig
C
Kaplan
Allan S
AS
Keel
Pamela K
PK
Klump
Kelly L
KL
La Via
Maria
M
Mitchell
James E
JE
Strober
Michael
M
Rotondo
Alessandro
A
Treasure
Janet
J
Woodside
D Blake
DB
D000293:Adolescent; D000328:Adult; D000368:Aged; D000856:Anorexia Nervosa / Q000235:genetics*; D002032:Bulimia / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055815:Young Adult
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