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Submitted on October 3, 2005
Accepted on December 27, 2005
The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, P R China; Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, NE 68131, USA; Department of Orthopedic Surgery, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108; Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, P R China
* To whom correspondence should be addressed. E-mail: dengh{at}umkc.edu.
Context: Age at menarche (AAM) is an important anthropological variable, which has major implication for a woman's health later in life. Genetic influence has been shown to contribute greatly to AAM, but the specific genetic determinants are largely unknown.
Objective: To identify the quantitative trait loci (QTL) underlying the variation in AAM.
Methods: We performed a large-scale genomewide linkage scan in 2,461 Caucasian women from 402 pedigrees. All the subjects were genotyped with 410 microsatellite markers spaced 
8.9 cM apart across the human genome. Using the variance component method, we conducted multipoint linkage analyses and two-locus tests for epistatic interaction.
Results: The strongest linkage signal was obtained at the genomic region of 22q13 (LOD = 3.70), the other two suggestive linkage was on 22q11 (LOD = 2.68) and 11q23 (LOD = 1.98), respectively. We also detected significant epistatic interaction between genomic regions of 22q13 and 3q13.
Conclusions: The identification of QTL and epistatic interaction in a large female sample, laid a foundation for further independent replication and fine-mapping studies as well as for positional and functional candidate gene studies, aiming at eventually finding the causal genetic variants and hidden mechanisms concerning the variation in AAM.
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