Runs of homozygosity identify a recessive locus 12q21.31 for human adult height.
BACKGROUND
Runs of homozygosity (ROHs) have recently been proposed to have potential recessive significance for complex traits. Human adult height is a classic complex trait with heritability estimated up to 90%, and recessive loci that contribute to adult height variation have been identified.


METHODS
Using the Affymetrix 500K array set, we performed a genome-wide ROHs analysis to identify genetic loci for adult height in a discovery sample including 998 unrelated Caucasian subjects from the midwest United States. For the significant ROHs identified, we replicated these findings in a family-based sample of 8385 Caucasian subjects from the Framingham Heart Study (FHS).


RESULTS
Our results revealed one ROH, located in 12q21.31, that had a strong association with adult height variation both in the discovery (P=6.69x10(-6)) and replication samples (P=5.40x10(-5)). We further validated the presence of this ROH using the HapMap sample.


CONCLUSIONS
Our findings open a new avenue for identifying loci with recessive contributions to adult height variation. Further molecular and functional studies are needed to explore and clarify the potential mechanism.
Yang
Tie-Lin
TL
Key Laboratory of Biomedical Information Engineering, 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.
Guo
Yan
Y
Zhang
Li-Shu
LS
Tian
Qing
Q
Yan
Han
H
Papasian
Christopher J
CJ
Recker
Robert R
RR
Deng
Hong-Wen
HW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001827:Body Height / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
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