A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci

Yukinori Okada, Yoichiro Kamatani, Atsushi Takahashi, Koichi Matsuda, Naoya Hosono, Hiroko Ohmiya, Yataro Daigo, Kazuhiko Yamamoto, Michiaki Kubo, Yusuke Nakamura, Naoyuki Kamatani

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Abstract

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 × 1028). Of these, the association to the LHX3-QSOX2 locus was entirely novel (rs12338076, P = 2.2 × 10-8 We also identified the association to the IGF1 locus (rs17032362, P = 8.1 × 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 × 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 × 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.

Original languageEnglish
Article numberddq091
Pages (from-to)2303-2312
Number of pages10
JournalHuman molecular genetics
Volume19
Issue number11
DOIs
Publication statusPublished - 26-02-2010

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Genome-Wide Association Study
Population
Gene Frequency
Alleles
Genome
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Okada, Y., Kamatani, Y., Takahashi, A., Matsuda, K., Hosono, N., Ohmiya, H., ... Kamatani, N. (2010). A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci. Human molecular genetics, 19(11), 2303-2312. [ddq091]. https://doi.org/10.1093/hmg/ddq091
Okada, Yukinori ; Kamatani, Yoichiro ; Takahashi, Atsushi ; Matsuda, Koichi ; Hosono, Naoya ; Ohmiya, Hiroko ; Daigo, Yataro ; Yamamoto, Kazuhiko ; Kubo, Michiaki ; Nakamura, Yusuke ; Kamatani, Naoyuki. / A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci. In: Human molecular genetics. 2010 ; Vol. 19, No. 11. pp. 2303-2312.
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abstract = "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 × 1028). Of these, the association to the LHX3-QSOX2 locus was entirely novel (rs12338076, P = 2.2 × 10-8 We also identified the association to the IGF1 locus (rs17032362, P = 8.1 × 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 × 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 × 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.",
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Okada, Y, Kamatani, Y, Takahashi, A, Matsuda, K, Hosono, N, Ohmiya, H, Daigo, Y, Yamamoto, K, Kubo, M, Nakamura, Y & Kamatani, N 2010, 'A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci', Human molecular genetics, vol. 19, no. 11, ddq091, pp. 2303-2312. https://doi.org/10.1093/hmg/ddq091

A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci. / Okada, Yukinori; Kamatani, Yoichiro; Takahashi, Atsushi; Matsuda, Koichi; Hosono, Naoya; Ohmiya, Hiroko; Daigo, Yataro; Yamamoto, Kazuhiko; Kubo, Michiaki; Nakamura, Yusuke; Kamatani, Naoyuki.

In: Human molecular genetics, Vol. 19, No. 11, ddq091, 26.02.2010, p. 2303-2312.

Research output: Contribution to journalArticle

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T1 - A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci

AU - Okada, Yukinori

AU - Kamatani, Yoichiro

AU - Takahashi, Atsushi

AU - Matsuda, Koichi

AU - Hosono, Naoya

AU - Ohmiya, Hiroko

AU - Daigo, Yataro

AU - Yamamoto, Kazuhiko

AU - Kubo, Michiaki

AU - Nakamura, Yusuke

AU - Kamatani, Naoyuki

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Okada Y, Kamatani Y, Takahashi A, Matsuda K, Hosono N, Ohmiya H et al. A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci. Human molecular genetics. 2010 Feb 26;19(11):2303-2312. ddq091. https://doi.org/10.1093/hmg/ddq091