A genome-wide association study on common SNPs and rare CNVs in anorexia nervosa
| Autor: | Nicholas Schork, Eleftheria Zeggini, Elena Tenconi, Cynthia Bulik, Raquel Rabionet, Xavier Estivill, Julia Huemer, Pieternella Slagboom, FERNANDO FERNANDEZ-ARANDA, Stephanie Le Hellard, Marion Roberts, Andrew Bergen, Federica Tozzi, André Scherag, Cinnamon Bloss, Pamela Keel |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Anorexia Nervosa Adolescent DNA Copy Number Variations Genotype Genome-wide association study Single-nucleotide polymorphism Biology Bioinformatics Polymorphism Single Nucleotide White People 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Receptors Opioid delta mental disorders SNP Humans Genetic Predisposition to Disease Copy-number variation Genetic risk Child Molecular Biology 030304 developmental biology Genetics 0303 health sciences Case-control study 3. Good health Psychiatry and Mental health Anorexia nervosa (differential diagnoses) Case-Control Studies Female 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Molecular psychiatry. 16(9) |
| ISSN: | 1476-5578 |
| Popis: | Anorexia nervosa (AN) is a mental illness with high mortality that most commonly afflicts adolescent female individuals. Clinical symptoms include chronic food refusal, weight loss and body image distortions. We carried out a genome-wide association study on 1033 AN cases and 3733 pediatric control subjects, all of whom were of European ancestry and were genotyped on the Illumina HumanHap610 platform (Illumina, San Diego, CA, USA). We confirmed that common single-nucleotide polymorphisms (SNPs) within OPRD1 (rs533123, P=0.0015) confer risk for AN, and obtained suggestive evidence that common SNPs near HTR1D (rs7532266, P=0.04) confer risk for restricting-type AN specifically. However, no SNPs reached genome-wide significance in our data, whereas top association signals were detected near ZNF804B, CSRP2BP, NTNG1, AKAP6 and CDH9. In parallel, we performed genome-wide analysis on copy number variations (CNVs) using the signal intensity data from the SNP arrays. We did not find evidence that AN cases have more CNVs than control subjects, nor do they have over-representation of rare or large CNVs. However, we identified several regions with rare CNVs that were only observed in AN cases, including a recurrent 13q12 deletion (1.5 Mb) disrupting SCAS in two cases, and CNVs disrupting the CNTN6/CNTN4 region in several AN cases. In conclusion, our study suggests that both common SNPs and rare CNVs may confer genetic risk to AN. These results point to intriguing genes that await further validation in independent cohorts for confirmatory roles in AN. |
| Databáze: | OpenAIRE |
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