0
Original Research: SARCOIDOSIS |

A Genome-Wide Linkage Analysis in 181 German Sarcoidosis Families Using Clustered Biallelic Markers

Annegret Fischer, PhD; Michael Nothnagel, PhD; Manfred Schürmann, MD; Joachim Müller-Quernheim, MD; Stefan Schreiber, MD; Sylvia Hofmann, PhD
Author and Funding Information

From the Institute of Clinical Molecular Biology (Drs Fischer and Hofmann), the Institute of Medical Informatics and Statistics (Dr Nothnagel), and the Institute of Clinical Molecular Biology and Department of General Internal Medicine, University Hospital Schleswig-Holstein (Dr Schreiber), Christian-Albrechts University, Kiel; the Institute of Human Genetics (Dr Schürmann), University of Lübeck, Lübeck; and the Department of Pneumology (Dr Müller-Quernheim), University of Freiburg, Freiburg, Germany.

Correspondence to: Stefan Schreiber, MD, Institute of Clinical Molecular Biology and Department of General Internal Medicine, University Hospital Schleswig-Holstein, Christian-Albrechts University, Schittenhelmstrasse 12, 24105, Kiel, Germany; e-mail: s.schreiber@mucosa.de


Funding/Support: The study was supported by the German Ministry of Education and Research (BMBF) through the National Genome Research Network [NGFN 01GS0809]. It received infrastructure support through the DFG excellence cluster “Inflammation at Interfaces.”

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;138(1):151-157. doi:10.1378/chest.09-2526
Text Size: A A A
Published online

Background:  Sarcoidosis (SA) is a systemic granulomatous inflammatory disorder with complex etiology and strong clustering in families. Genome-wide association studies have been successful in the identification of common risk variants for the disease. To reveal susceptibility variants with low frequencies but strong effects, we performed a genome-wide linkage scan in a large sample of SA families.

Methods:  We genotyped 528 members of 181 German SA families for 3,882 single nucleotide polymorphism assays from the SNPlex System Human Linkage Mapping Set 4K.

Results:  Nonparametric linkage analysis revealed one region of suggestive linkage on chromosome 12p13.31 at 20 cM (logarithm of odds [LOD] = 2.53; local P value = .0003) and another linkage peak of nearly suggestive linkage on 9q33.1 at 134 cM (LOD = 2.12; local P value = .0009). The latter has been reported to show suggestive evidence for linkage in a sample of 229 African American SA families previously. Analysis of acute and chronically affected families revealed a subphenotype-specific linkage pattern and an additional, nearly suggestive linkage peak on chromosome 16p13.11 at 38 cM (LOD = 2.09; local P value = .001), which was confined to acute SA.

Conclusion:  Our results propose that the respective regions might harbor yet-unidentified, possibly subphenotype-specific risk factors for the disease (eg, with immune-related functions like the tumor necrosis factor receptor 1). They should be proved to be important for SA pathogenesis and investigated in detail with an emphasis on rare variants. Subphenotype-specific risk factors might serve for prognosis of the clinical course of the disease.

Figures in this Article

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543