Genomewide linkage scan for quantitative trait loci underlying variation in age at menarche.
BACKGROUND
Age at menarche (AAM) is an important anthropological variable that has major implications 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
The objective of this study was to identify the quantitative trait loci (QTL) underlying the variations in AAM.


METHODS
We performed a large-scale, genomewide, linkage scan in 2461 Caucasian women from 402 pedigrees. All subjects were genotyped with 410 microsatellite markers spaced approximately 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 linkages were on 22q11 (LOD, 2.68) and 11q23 (LOD, 1.98), respectively. We also detected significant epistatic interaction between genomic regions 22q13 and 3q13.


CONCLUSIONS
The identification of QTL and epistatic interaction in a large female sample laid a foundation for independent replication and fine-mapping studies as well as positional and functional candidate gene studies aimed at finding the causal genetic variants and hidden mechanisms concerning the variations in AAM.
Guo
Yan
Y
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, People's Republic of China.
Shen
Hui
H
Xiao
Peng
P
Xiong
Dong-Hai
DH
Yang
Tie-Lin
TL
Guo
Yan-Fang
YF
Long
Ji-Rong
JR
Recker
Robert R
RR
Deng
Hong-Wen
HW
D000367:Age Factors; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002892:Chromosomes, Human, Pair 22; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008297:Male; D008572:Menarche / Q000235:genetics* / Q000502:physiology; D010375:Pedigree; D040641:Quantitative Trait Loci; D044465:White People / Q000235:genetics
D005819:Genetic Markers