A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci.
Previous genome-wide association studies (GWASs) have identified several loci associated with human height; however, such evidence was mostly reported in Caucasian populations. Since the different distributions of height between populations suggest their different genetic backgrounds, analysis in different populations would be useful. Here, we present the results of a GWAS for adult height in 19 633 Japanese subjects. We found eight significantly associated loci that satisfied the genome-wide significance level (P < 5.0 x 10(-8)). Of these, the association to the LHX3-QSOX2 locus was entirely novel (rs12338076, P = 2.2 x 10(-8)). We also identified the association to the IGF1 locus (rs17032362, P = 8.1 x 10(-9)). Conditional association analysis in the IGF1 locus with rs17032362 suggested the existence of an additional independent association with height to this locus (rs1457595, P = 1.2 x 10(-5)). We observed large differences in the allele frequencies of rs17032362 and rs1457595 between Japanese (34 and 9%, respectively) and Caucasian (1.7 and 0%, respectively) populations, thereby suggesting weak statistical powers for the IGF1 locus in the previous Caucasian GWASs for height. We extensively compared our results with those of previous reports on the Caucasian and Korean populations. We were able to replicate all four loci previously reported in Koreans (EFEMP1, ZBTB38, HMGA1 and PLAG1, P < 5.0 x 10(-8)) and 15 loci identified in Caucasians (P < 0.001). The combination of the height-associated loci identified in our study and the previous GWASs demonstrated an effect size of 1.26 cm (95% confidence interval: 1.18-1.34) per 1.0 increase of the normalized Z score for height-increasing alleles, explaining 4.6% of the total variance of adult height.
Okada
Yukinori
Y
Center for Genomic Medicine, Institute of Physical and Chemical Research, RIKEN, Kanagawa, Japan.
Kamatani
Yoichiro
Y
Takahashi
Atsushi
A
Matsuda
Koichi
K
Hosono
Naoya
N
Ohmiya
Hiroko
H
Daigo
Yataro
Y
Yamamoto
Kazuhiko
K
Kubo
Michiaki
M
Nakamura
Yusuke
Y
Kamatani
Naoyuki
N
D000328:Adult; D044466:Asian People / Q000235:genetics*; D001827:Body Height / Q000235:genetics*; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D060850:LIM-Homeodomain Proteins; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014157:Transcription Factors; D044465:White People / Q000235:genetics
D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C094898:Lhx3 protein; D014157:Transcription Factors; D007334:Insulin-Like Growth Factor I; D050862:Oxidoreductases Acting on Sulfur Group Donors; C481160:QSOX2 protein, human