Single nucleotide polymorphism-based genome-wide linkage analysis in Japanese atopic dermatitis families

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Abstract

Background

Atopic dermatitis develops as a result of complex interactions between several genetic and environmental factors. To date, 4 genome-wide linkage studies of atopic dermatitis have been performed in Caucasian populations, however, similar studies have not been done in Asian populations. The aim of this study was to identify chromosome regions linked to atopic dermatitis in a Japanese population.

Methods

We used a high-density, single nucleotide polymorphism genotyping assay, the Illumina BeadArray Linkage Mapping Panel (version 4) comprising 5,861 single nucleotide polymorphisms, to perform a genome-wide linkage analysis of 77 Japanese families with 111 affected sib-pairs with atopic dermatitis.

Results

We found suggestive evidence for linkage with 15q21 (LOD = 2.01, NPL = 2.87, P = .0012) and weak linkage to 1q24 (LOD = 1.26, NPL = 2.44, P = .008).

Conclusion

We report the first genome-wide linkage study of atopic dermatitis in an Asian population, and novel loci on chromosomes 15q21 and 1q24 linked to atopic dermatitis. Identification of novel causative genes for atopic dermatitis will advance our understanding of the pathogenesis of atopic dermatitis.

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Most cited references 32

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Efficiency and power in genetic association studies.

Paul de Bakker, Roman Yelensky, Itsik Pe'er … (2005)

We investigated selection and analysis of tag SNPs for genome-wide association studies by specifically examining the relationship between investment in genotyping and statistical power. Do pairwise or multimarker methods maximize efficiency and power? To what extent is power compromised when tags are selected from an incomplete resource such as HapMap? We addressed these questions using genotype data from the HapMap ENCODE project, association studies simulated under a realistic disease model, and empirical correction for multiple hypothesis testing. We demonstrate a haplotype-based tagging method that uniformly outperforms single-marker tests and methods for prioritization that markedly increase tagging efficiency. Examining all observed haplotypes for association, rather than just those that are proxies for known SNPs, increases power to detect rare causal alleles, at the cost of reduced power to detect common causal alleles. Power is robust to the completeness of the reference panel from which tags are selected. These findings have implications for prioritizing tag SNPs and interpreting association studies.

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Atopic dermatitis.

Donald Leung, Thomas Bieber (2003)

Atopic dermatitis is a highly pruritic chronic inflammatory skin disorder affecting 10-20% of children worldwide. Symptoms can persist or begin in adulthood. It is also the most common cause of occupational skin disease in adults. This disease results from an interaction between susceptibility genes, the host's environment, pharmacological abnormalities, skin barrier defects, and immunological factors. New management approaches have evolved from advances in our understanding of the pathobiology of this common skin disorder.

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Lymphocyte homing and homeostasis.

E C Butcher, L J Picker (1996)

The integration and control of systemic immune responses depends on the regulated trafficking of lymphocytes. This lymphocyte "homing" process disperses the immunologic repertoire, directs lymphocyte subsets to the specialized microenvironments that control their differentiation and regulate their survival, and targets immune effector cells to sites of antigenic or microbial invasion. Recent advances reveal that the exquisite specificity of lymphocyte homing is determined by combinatorial "decision processes" involving multistep sequential engagement of adhesion and signaling receptors. These homing-related interactions are seamlessly integrated into the overall interaction of the lymphocyte with its environment and participate directly in the control of lymphocyte function, life-span, and population dynamics. In this article a review of the molecular basis of lymphocyte homing is presented, and mechanisms by which homing physiology regulated the homeostasis of immunologic resources are proposed.

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Author and article information

Journal

Journal ID (nlm-ta): BMC Dermatol

Title: BMC Dermatology

Publisher: BioMed Central

ISSN (Electronic): 1471-5945

Publication date Collection: 2007

Publication date (Electronic): 28 September 2007

Volume: 7

Page: 5

Affiliations

[1 ]Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan

[2 ]Mito Saiseikai General Hospital, Japan

[3 ]Department of Dermatology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan

[4 ]Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan

[5 ]Mito Red Cross Hospital, Japan

[6 ]Ibaraki Prefectural Central Hospital, Japan

[7 ]Department of Pediatrics, Tsukuba Medical Center Hospital, Japan

[8 ]Department of Public Health, Chiba University Graduate School of Medicine, Japan

[9 ]Laboratory of Genetics of Allergic Disease, RIKEN SNP Research Center, Yokohama, Japan

Article

Publisher ID: 1471-5945-7-5

DOI: 10.1186/1471-5945-7-5

PMC ID: 2082241

PubMed ID: 17900373

SO-VID: e7dec8b3-c1b2-46da-8565-612cdb28f3fe

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 24 April 2007

Date accepted : 28 September 2007

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Single nucleotide polymorphism-based genome-wide linkage analysis in Japanese atopic dermatitis families

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Abstract

Background

Methods

Results

Conclusion

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Karger: Dermatology

Most cited references 32

Efficiency and power in genetic association studies.

Atopic dermatitis.

Lymphocyte homing and homeostasis.

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Cited by 2

Most referenced authors 853