Association study of 182 candidate genes in anorexia nervosa

Andrea Poyastro Pinheiro, Cynthia M. Bulik, Laura M. Thornton, Patrick F. Sullivan, Tammy L. Root, Cinnamon S. Bloss, Wade H. Berrettini, Nicholas J. Schork, Walter H. Kaye, Andrew W. Bergen, Pierre Magistretti, Harry Brandt, Steve Crawford, Scott Crow, Manfred M. Fichter, David Goldman, Katherine A. Halmi, Craig Johnson, Allan S. Kaplan, Pamela K. KeelKelly L. Klump, Maria La Via, James E. Mitchell, Michael Strober, Alessandro Rotondo, Janet Treasure, D. Blake Woodside

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1070-1080
Number of pages11
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume153
Issue number5
DOIs
StatePublished - Jul 2010

Keywords

  • Anorexia nervosa
  • Bulimia nervosa
  • Probands
  • Single nucleotide polymorphisms

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