Epistasis between QTLs for bone density variation in Copenhagen x dark agouti F2 rats

Daniel L. Koller, Lixiang Liu, Imranul Alam, Qiwei Sun, Michael Econs, Tatiana Foroud, Charles H. Turner

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The variation in several of the risk factors for osteoporotic fracture, including bone mineral density (BMD), has been shown to be strongly influenced by genetic differences. However, the genetic architecture of BMD is complex in both humans and in model organisms. We previously reported quantitative trait locus (QTL) results for BMD from a genome screen of 828 F2 progeny of Copenhagen and dark agouti rats. These progeny also provide an excellent opportunity to search for epistatic effects, or interaction between genetic loci, that contribute to fracture risk. Microsatellite marker data from a 20-cM genome screen was analyzed along with weight-adjusted bone density (DXA and pQCT) phenotypic data using the R/qtl software package. Genotype and phenotype data were permuted to determine genome-wide significance thresholds for the full model and epistasis (interaction) LOD scores corresponding to an alpha level of 0.01. A novel locus on chromosome 15 and a previously reported chromosome 14 QTL demonstrated a strong epistatic effect on BMD at the femur by DXA (LOD = 5.4). Two novel QTLs on chromosomes 2 and 12 were found to interact to affect total BMD at the femur midshaft by pQCT (LOD = 5.0). These results provide new information regarding the mode of action of previously identified QTL in the rat, as well as identifying novel loci that act in combination with known QTL or with other novel loci to contribute to BMD variation.

Original languageEnglish
Pages (from-to)180-186
Number of pages7
JournalMammalian Genome
Volume20
Issue number3
DOIs
StatePublished - Mar 2009

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Bone Density
Quantitative Trait Loci
Genome
Femur
Chromosomes, Human, Pair 15
Chromosomes, Human, Pair 14
Chromosomes, Human, Pair 12
Osteoporotic Fractures
Genetic Loci
Chromosomes, Human, Pair 2
Dasyproctidae
Microsatellite Repeats
Software
Genotype
Phenotype
Weights and Measures

ASJC Scopus subject areas

  • Genetics

Cite this

Epistasis between QTLs for bone density variation in Copenhagen x dark agouti F2 rats. / Koller, Daniel L.; Liu, Lixiang; Alam, Imranul; Sun, Qiwei; Econs, Michael; Foroud, Tatiana; Turner, Charles H.

In: Mammalian Genome, Vol. 20, No. 3, 03.2009, p. 180-186.

Research output: Contribution to journalArticle

Koller, Daniel L. ; Liu, Lixiang ; Alam, Imranul ; Sun, Qiwei ; Econs, Michael ; Foroud, Tatiana ; Turner, Charles H. / Epistasis between QTLs for bone density variation in Copenhagen x dark agouti F2 rats. In: Mammalian Genome. 2009 ; Vol. 20, No. 3. pp. 180-186.
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