Genome-wide linkage scan to detect loci influencing levels of dehydroepiandrosterones in the HERITAGE Family Study

A genome-wide linkage scan was performed to identify genomic regions that i nfluence levels of dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and DHEA fatty acid esters (DHEA-FA) at baseline and in response to 20 weeks o f endurance exercise training in sedentary white and black participants in the HERITAGE Family Study. The baseline levels were log-transformed and adj usted for the effects of age and sex prior to genetic analysis. The trainin g responses were adjusted for the effects of age, sex, and the baseline val ues. A total of 509 autosomal component polymorphic markers were used for t he genome scan with an average spacing of 6.0 Mb. Multipoint variance compo nents linkage analyses were performed in nuclear families containing 360 wh ite and 106 black sibling pairs. We found 5 genomic regions with significan t linkages for baseline DHEA-FA in whites, with log odd (LOD) scores over 3 .6 (P < 2 x 10(-5)). They include (1) D1S468 (LOD 4.56,2.533 Mb, 1p36.22); (2) D2S177 (LOD 5.65,52.663 Mb, 2p16.3); (3) D4S2397 (LOD 3.98,32.246 Mb, 4 p15.2); (4) the paraoxonase loci (LOD 3.93 similar to3.99,101.544 similar t o 102.933 Mb, 7q21.3), and D7S821 (LOD 3.88,104.497 Mb, 7q22.1); and (5) D1 2S372 (LOD 4.66,2.129 Mb, 12q13.33). In addition, we obtained evidence of s uggestive linkages (2.2 < LOD < 3.6; 2 x 10(-5) < P < 7 x 10(-4)) on chromo somes 3p, 6q, and 8q for baseline DHEAS; on chromosomes 2q, 3p, 9q, 10p, 16 q, and 17p for baseline DHEA-FA in whites; and on chromosomes 9q and 11p fo r baseline DHEA in blacks. This is the first genome-wide linkage scan searc hing for genomic regions influencing human DHEA levels. Several potential c andidate genes are located in these genomic regions, which warrant further studies in HERITAGE and other cohorts. Copyright (C) 2001 by W.B. Saunders Company.