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| Mapping determinants of human gene expression by regional and genome-wide association |
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| Author(s): Cheung VG, Spielman RS, Ewens KG, Weber TM, Morley M, Burdick JT |
| Source: NATURE Volume: 437 Issue: 7063 Pages: 1365-1369 Published: OCT 27 2005 |
| Times Cited: 215 References: 22 |
| Abstract: To study the genetic basis of natural variation in gene expression, we previously carried out genome-wide linkage analysis and mapped the determinants of similar to 1,000 expression phenotypes(1). In the present study, we carried out association analysis with dense sets of single-nucleotide polymorphism ( SNP) markers from the International HapMap Project(2). For 374 phenotypes, the association study was performed with markers only from regions with strong linkage evidence; these regions all mapped close to the expressed gene. For a subset of 27 phenotypes, analysis of genome-wide association was performed with > 770,000 markers. The association analysis with markers under the linkage peaks confirmed the linkage results and narrowed the candidate regulatory regions for many phenotypes with strong linkage evidence. The genome-wide association analysis yielded highly significant results that point to the same locations as the genome scans for about 50% of the phenotypes. For one candidate determinant, we carried out functional analyses and confirmed the variation in cis-acting regulatory activity. Our findings suggest that association studies with dense SNP maps will identify susceptibility loci or other determinants for some complex traits or diseases. |
| Document Type: Article |
| Language: English |
| Reprint Address: Cheung, VG (reprint author), Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA |
Addresses:
1. Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA
2. Univ Penn, Dept Genet, Philadelphia, PA 19104 USA
3. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 977UQ |
| ISSN: 0028-0836 |
| DOI: 10.1038/nature04244 |
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