1. ¹Division of Pulmonary, Critical Care, and Sleep Medicine, Mount Sinai School of Medicine, New York, NY, USA
2. ²Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA
3. ³Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, OH, USA
4. ⁴Pulmonary Division, School of Medicine, University of North Carolina, Chapel Hill, NC, USA
5. ⁵George Washington University Biostatistics Center, Washington, DC, USA
6. ⁶Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston, SC, USA
7. ⁷Pulmonary and Critical Care Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA
8. ⁸Department of Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, MI, USA
9. ⁹Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
10. ¹⁰Division of Environmental and Occupational Health Sciences, National Jewish Medical and Research Center, Denver, CO, USA
11. ¹¹Department of Family Medicine and Community Health Care Studies, Georgetown University, Washington, DC, USA
12. ¹²University of Pennsylvania Medical Center Pulmonary and Critical Care Division, Philadelphia, PA, USA

Correspondence: Dr MC Iannuzzi, Pulmonary, Critical Care and Sleep Medicine, Mount Sinai Medical Center, 1 Gustave Levy Place Box 1232, New York, New York 10029, USA. E-mail: Michael.Iannuzzi@mssm.edu

Received 3 March 2005; Revised 27 April 2005; Accepted 28 April 2005; Published online 9 June 2005.

Abstract

Sarcoidosis, a systemic granulomatous disease of unknown etiology, likely results from an environmental insult in a genetically susceptible host. In the US, African Americans are more commonly affected with sarcoidosis and suffer greater morbidity than Caucasians. We searched for sarcoidosis susceptibility loci by conducting a genome-wide, sib pair multipoint linkage analysis in 229 African-American families ascertained through two or more sibs with a history of sarcoidosis. Using the Haseman–Elston regression technique, linkage peaks with P-values less than 0.05 were identified on chromosomes 1p22, 2p25, 5p15-13, 5q11, 5q35, 9q34, 11p15 and 20q13 with the most prominent peak at D5S2500 on chromosome 5q11 (P=0.0005). We found agreement for linkage with the previously reported genome scan of a German population at chromosomes 1p and 9q. Based on the multiple suggestive regions for linkage found in our study population, it is likely that more than one gene influences sarcoidosis susceptibility in African Americans. Fine mapping of the linked regions, particularly on chromosome 5q, should help to refine linkage signals and guide further sarcoidosis candidate gene investigation.