Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture.
BACKGROUND
Osteoporotic fracture (OF) as a clinical endpoint is a major complication of osteoporosis. To screen for OF susceptibility genes, we performed a genome-wide association study and carried out de novo replication analysis of an East Asian population.


METHODS
Association was tested using a logistic regression analysis. A meta-analysis was performed on the combined results using effect size and standard errors estimated for each study.


RESULTS
In a combined meta-analysis of a discovery cohort (288 cases and 1139 controls), three hospital based sets in replication stage I (462 cases and 1745 controls), and an independent ethnic group in replication stage II (369 cases and 560 for controls), we identified a new locus associated with OF (rs784288 in the MECOM gene) that showed genome-wide significance (p=3.59×10(-8); OR 1.39). RNA interference revealed that a MECOM knockdown suppresses osteoclastogenesis.


CONCLUSIONS
Our findings provide new insights into the genetic architecture underlying OF in East Asians.
Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Republic of Korea.
Joo-Yeon
JY
Hwang
Seung Hun
SH
Lee
Min Jin
MJ
Go
Beom-Jun
BJ
Kim
Ikuyo
I
Kou
Shiro
S
Ikegawa
Yan
Y
Guo
Hong-Wen
HW
Deng
Soumya
S
Raychaudhuri
Young Jin
YJ
Kim
Ji Hee
JH
Oh
Youngdoe
Y
Kim
Sanghoon
S
Moon
Dong-Joon
DJ
Kim
Heejo
H
Koo
My-Jung
MJ
Cha
Min Hye
MH
Lee
Ji Young
JY
Yun
Hye-Sook
HS
Yoo
Young-Ah
YA
Kang
Eun-Hee
EH
Cho
Sang-Wook
SW
Kim
Ki Won
KW
Oh
Moo Il
MI
Kang
Ho Young
HY
Son
Shin-Yoon
SY
Kim
Ghi Su
GS
Kim
Bok-Ghee
BG
Han
Yoon Shin
YS
Cho
Myeong-Chan
MC
Cho
Jong-Young
JY
Lee
Jung-Min
JM
Koh
D000368:Aged; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D000074008:MDS1 and EVI1 Complex Locus Protein; D008875:Middle Aged; D010012:Osteogenesis / Q000235:genetics; D010024:Osteoporosis / Q000235:genetics* / Q000473:pathology; D058866:Osteoporotic Fractures / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011519:Proto-Oncogenes / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D014157:Transcription Factors