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A Follow-Up Linkage Study for Quantitative Trait Loci Contributing to Obesity-Related Phenotypes

Osteoporosis Research Center (Y.-J.L., F.-H.X., H.S., Y.-Z.L., H.-Y.D., L-J.Z., Q.-Y.H., V.D., T.C., K.M.D., R.R.R., H.-W.D.) and Department of Biomedical Sciences (Y.-J.L., F.-H.X., H.S., Y.-Z.L., L.-J.Z., H.-W.D.), Creighton University, Omaha, Nebraska 68131; Laboratory of Molecular and Statistical Genetics (H.-W.D.), College of Life Sciences Hunan Normal University, Changsha, 410081 Hunan, China; and Center for Medical Informatics (J.-L.L.), School of Medicine, Yale University, New Haven, Connecticut 06520-8009

Address all correspondence and requests for reprints to: Hong-Wen Deng, Ph.D., Osteoporosis Research Center, Creighton University, 601 North 30th Street, Suite 6787, Omaha, Nebraska 68131. E-mail: deng{at}creighton.edu.

We have recently reported a whole-genome scan in a sample of 630 subjects from 53 extended pedigrees, in which several genomic regions that may contain quantitative trait loci (QTLs) for obesity were suggested. In the present study, with an attempt to confirm our previous findings, we performed a follow-up linkage study in an expanded sample of 79 pedigrees with 1816 subjects (including expanded previous 53 pedigrees and 26 newly recruited pedigrees containing 1058 subjects). A new set of microsatellite markers spanning previously identified regions were selected, with the average genomic distance narrowed from approximately 10 cM to approximately 5 cM in this study. Using a variance component method, we performed two- and multipoint linkage analyses in the following three sample sets: expanded previous 53 pedigrees (758 subjects), 26 new pedigrees, and 79 total pedigrees. For body mass index, analyses of the expanded 53 pedigrees attained a LOD score of 2.32 near marker D1S468 in two-point analysis and a maximum LOD score (MLS) of 2.21 in multipoint analysis; 2q14 near marker D2S347 attained a LOD score of 3.42 in two-point analysis and a MLS of 3.93 in multipoint analysis. The linkage peaks at 1p36 and 2q14 were further supported in the analyses of all 79 pedigrees, with multipoint MLS being 1.38 and 0.90, respectively. For fat mass, genomic region 6q27 achieved a LOD score of 1.24 in two-point analysis and an MLS of 0.92 in multipoint analysis in all 79 pedigrees. Our data support that 1p36, 2q14, and 6q27 are promising regions that may harbor QTLs for obesity phenotypes.

This work was supported in part by grants from Health Future Foundation, National Institutes of Health Grants K01 AR02170-01, R01 AR45349-01, R01 GM60402-01A1, and P01 DC01813-07, grants from the State of Nebraska Cancer and Smoking Related Disease Research Program and the State of Nebraska Tobacco Settlement Fund, United States Department of Energy Grant DE-FG03-00ER63000/A00, Creighton University, grants from the National Science Foundation of China, a grant from the Huo Ying Dong Education Foundation, and grants from HuNan Normal University and the Ministry of Education of China.

Abbreviations: BMD, Bone mineral density; BMI, body mass index; DXA, dual x-ray absorptiometry; IBD, identity by descent; MLS, maximum LOD score; PFM, percentage fat mass; QTL, quantitative trait locus.

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