1. ¹Department of Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, MI, USA
2. ²Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA
3. ³Division of Pulmonary, Critical Care, and Sleep Medicine, Mount Sinai School of Medicine, New York, NY, USA

Correspondence: Dr BA Rybicki, Department of Biostatistics and Research Epidemiology, Henry Ford Health System, 1 Ford Place, 3E, Detroit, MI 48202, USA. E-mail: brybick1@hfhs.org

⁴See online supplementary information.

Received 22 November 2006; Revised 2 April 2007; Accepted 4 April 2007; Published online 3 May 2007.

Abstract

The sarcoidosis genetic analysis (SAGA) study previously identified eight chromosomal regions with suggestive evidence for linkage to sarcoidosis susceptibility in African-American sib pairs. Since the clinical course of sarcoidosis is variable and likely under genetic control, we used the affected relative pair portion of the SAGA sample (n=344 pairs) to perform multipoint linkage analyses with covariates based on pulmonary and organ involvement phenotypes. Chest radiographic resolution was the pulmonary phenotype with the highest LOD (logarithm of the backward odds, or likelihood ratio) score of 5.11 at D1S3720 on chromosome 1p36 (P=4 10^-5). In general, higher LOD scores were attained for covariates that modeled clustered organ system involvement rather than individual organ systems, with the cardiac/renal group having the highest LOD score of 6.65 at chromosome 18q22 (P=2 10^-5). The highest LOD scores for the other three organ involvement groups of liver/spleen/bone marrow, neuro/lymph and ocular/skin/joint were 3.72 at 10p11 (P=0.0004), 5.16 at 7p22 (P=4 10^-5) and 2.93 at 10q26 (P=0.001), respectively. Most of the phenotype linkages did not overlap with the regions previously found linked to susceptibility. Our results suggest that genes influencing clinical presentation of sarcoidosis in African Americans are likely to be different from those that underlie disease susceptibility.