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Identification of novel candidate loci for anorexia nervosa at 1q41 and 11q22 in Japanese by a genome-wide association analysis with microsatellite markers.

Abstract

The Japanese Genetic Research Group for Eating Disorders (JGRED) is a multisite collaborative study group that was organized for the systematic recruitment of patients with an eating disorder for the purpose of genetic study in Japan. We conducted a genome-wide case-control association study using 23 465 highly polymorphic microsatellite (MS) markers to identify genomic loci related to anorexia nervosa (AN). Pooled DNA typing in two screening stages, followed by individual typing of 320 AN cases and 341 controls, allowed us to identify 10 MS markers to be associated with AN. To narrow down genomic regions responsible for the association of these MS markers, we further conducted a single-nucleotide polymorphism (SNP) association analysis for 7 of the 10 loci in 331 AN cases and 872 controls, which include the 320 AN cases and the 341 controls genotyped in the MS screening, respectively. Two loci, namely 1q41 and 11q22, remained significantly associated with AN in the SNP-based fine mapping, indicating the success in narrowing down susceptibility regions for AN. Neither of these loci showed a positive evidence of association with bulimia nervosa. The most significant association was observed at SNP rs2048332 (allelic P-value=0.00023) located at 3'-downstream of the SPATA17 gene on the 1q41 locus. The association analysis for MS-SNP haplotypes detected a statistically significant association (permutation P-value=0.00003) of the A-4-G-T haplotype that comprised four SNP/MS markers (rs6590474-D11S0268i-rs737582-rs7947224) on the 11q22 locus with AN. This linkage disequilibrium block spanning a 20.2-kb interval contains exon 9 of the CNTN5 gene encoding contactin 5.

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Authors+Show Affiliations

,

Department of Pathology, Research Institute, International Medical Center of Japan, Shinjuku, Tokyo, Japan. knakabayashi@nch.go.jp

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Source

Journal of human genetics 54:9 2009 Sep pg 531-7

MeSH

Adult
Anorexia Nervosa
Asian Continental Ancestry Group
Case-Control Studies
Chromosome Mapping
Chromosomes, Human, Pair 1
Chromosomes, Human, Pair 11
Female
Genome, Human
Genome-Wide Association Study
Genotype
Humans
Linkage Disequilibrium
Male
Microsatellite Repeats
Polymorphism, Single Nucleotide
Young Adult

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19680270

Citation

Nakabayashi, Kazuhiko, et al. "Identification of Novel Candidate Loci for Anorexia Nervosa at 1q41 and 11q22 in Japanese By a Genome-wide Association Analysis With Microsatellite Markers." Journal of Human Genetics, vol. 54, no. 9, 2009, pp. 531-7.
Nakabayashi K, Komaki G, Tajima A, et al. Identification of novel candidate loci for anorexia nervosa at 1q41 and 11q22 in Japanese by a genome-wide association analysis with microsatellite markers. J Hum Genet. 2009;54(9):531-7.
Nakabayashi, K., Komaki, G., Tajima, A., Ando, T., Ishikawa, M., Nomoto, J., ... Shirasawa, S. (2009). Identification of novel candidate loci for anorexia nervosa at 1q41 and 11q22 in Japanese by a genome-wide association analysis with microsatellite markers. Journal of Human Genetics, 54(9), pp. 531-7. doi:10.1038/jhg.2009.74.
Nakabayashi K, et al. Identification of Novel Candidate Loci for Anorexia Nervosa at 1q41 and 11q22 in Japanese By a Genome-wide Association Analysis With Microsatellite Markers. J Hum Genet. 2009;54(9):531-7. PubMed PMID: 19680270.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of novel candidate loci for anorexia nervosa at 1q41 and 11q22 in Japanese by a genome-wide association analysis with microsatellite markers. AU - Nakabayashi,Kazuhiko, AU - Komaki,Gen, AU - Tajima,Atsushi, AU - Ando,Tetsuya, AU - Ishikawa,Mayuko, AU - Nomoto,Junko, AU - Hata,Kenichiro, AU - Oka,Akira, AU - Inoko,Hidetoshi, AU - Sasazuki,Takehiko, AU - ,, AU - Shirasawa,Senji, Y1 - 2009/08/14/ PY - 2009/8/15/entrez PY - 2009/8/15/pubmed PY - 2009/12/16/medline SP - 531 EP - 7 JF - Journal of human genetics JO - J. Hum. Genet. VL - 54 IS - 9 N2 - The Japanese Genetic Research Group for Eating Disorders (JGRED) is a multisite collaborative study group that was organized for the systematic recruitment of patients with an eating disorder for the purpose of genetic study in Japan. We conducted a genome-wide case-control association study using 23 465 highly polymorphic microsatellite (MS) markers to identify genomic loci related to anorexia nervosa (AN). Pooled DNA typing in two screening stages, followed by individual typing of 320 AN cases and 341 controls, allowed us to identify 10 MS markers to be associated with AN. To narrow down genomic regions responsible for the association of these MS markers, we further conducted a single-nucleotide polymorphism (SNP) association analysis for 7 of the 10 loci in 331 AN cases and 872 controls, which include the 320 AN cases and the 341 controls genotyped in the MS screening, respectively. Two loci, namely 1q41 and 11q22, remained significantly associated with AN in the SNP-based fine mapping, indicating the success in narrowing down susceptibility regions for AN. Neither of these loci showed a positive evidence of association with bulimia nervosa. The most significant association was observed at SNP rs2048332 (allelic P-value=0.00023) located at 3'-downstream of the SPATA17 gene on the 1q41 locus. The association analysis for MS-SNP haplotypes detected a statistically significant association (permutation P-value=0.00003) of the A-4-G-T haplotype that comprised four SNP/MS markers (rs6590474-D11S0268i-rs737582-rs7947224) on the 11q22 locus with AN. This linkage disequilibrium block spanning a 20.2-kb interval contains exon 9 of the CNTN5 gene encoding contactin 5. SN - 1435-232X UR - https://www.unboundmedicine.com/medline/citation/19680270/Identification_of_novel_candidate_loci_for_anorexia_nervosa_at_1q41_and_11q22_in_Japanese_by_a_genome_wide_association_analysis_with_microsatellite_markers_ DB - PRIME DP - Unbound Medicine ER -