A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1 locus in multiple ethnic groups

Douglas Londono, Ikuyo Kou, Todd A. Johnson, Swarkar Sharma, Yoji Ogura, Tatsuhiko Tsunoda, Atsushi Takahashi, Morio Matsumoto, John A. Herring, Tsz Ping Lam, Xingyan Wang, Elisa M S Tam, You Qiang Song, Yan Hui Fan, Danny Chan, Kathryn S E Cheah, Xusheng Qiu, Hua Jiang, Dongsheng Huang, Peiqiang SuPak Sham, Kenneth M C Cheung, Keith D K Luk, Derek Gordon, Yong Qiu, Jack Cheng, Nelson Tang, Shiro Ikegawa, Carol A. Wise

Research output: Contribution to journalArticle

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Abstract

Background: Adolescent idiopathic scoliosis (AIS) is a common rotational deformity of the spine that presents in children worldwide, yet its etiology is poorly understood. Recent genome-wide association studies (GWAS) have identified a few candidate risk loci. One locus near the chromosome 10q24.31 LBX1 gene (OMIM #604255) was originally identified by a GWAS of Japanese subjects and replicated in additional Asian populations. To extend this result, and to create larger AIS cohorts for the purpose of large-scale meta-analyses in multiple ethnicities, we formed a collaborative group called the International Consortium for Scoliosis Genetics (ICSG). Methods: Here, we report the first ICSG study, a metaanalysis of the LBX1 locus in six Asian and three non- Asian cohorts. Results: We find significant evidence for association of this locus with AIS susceptibility in all nine cohorts. Results for seven cohorts containing both genders yielded P=1.22-10-43 for rs11190870, and P=2.94-10-48 for females in all nine cohorts. Comparing the regional haplotype structures for three populations, we refined the boundaries of association to a ̃25 kb block encompassing the LBX1 gene. The LBX1 protein, a homeobox transcription factor that is orthologous to the Drosophila ladybird late gene, is involved in proper migration of muscle precursor cells, specification of cardiac neural crest cells, and neuronal determination in developing neural tubes. Conclusions: Our results firmly establish the LBX1 region as the first major susceptibility locus for AIS in Asian and non-Hispanic white groups, and provide a platform for larger studies in additional ancestral groups.

Original languageEnglish
Pages (from-to)401-406
Number of pages6
JournalJournal of Medical Genetics
Volume51
Issue number6
DOIs
Publication statusPublished - 2014

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Scoliosis
Ethnic Groups
Meta-Analysis
Genome-Wide Association Study
Genes
Genetic Databases
Homeodomain Proteins
Neural Tube
Neural Crest
Myoblasts
Haplotypes
Population
Drosophila
Spine
Transcription Factors
Chromosomes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Medicine(all)

Cite this

A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1 locus in multiple ethnic groups. / Londono, Douglas; Kou, Ikuyo; Johnson, Todd A.; Sharma, Swarkar; Ogura, Yoji; Tsunoda, Tatsuhiko; Takahashi, Atsushi; Matsumoto, Morio; Herring, John A.; Lam, Tsz Ping; Wang, Xingyan; Tam, Elisa M S; Song, You Qiang; Fan, Yan Hui; Chan, Danny; Cheah, Kathryn S E; Qiu, Xusheng; Jiang, Hua; Huang, Dongsheng; Su, Peiqiang; Sham, Pak; Cheung, Kenneth M C; Luk, Keith D K; Gordon, Derek; Qiu, Yong; Cheng, Jack; Tang, Nelson; Ikegawa, Shiro; Wise, Carol A.

In: Journal of Medical Genetics, Vol. 51, No. 6, 2014, p. 401-406.

Research output: Contribution to journalArticle

Londono, D, Kou, I, Johnson, TA, Sharma, S, Ogura, Y, Tsunoda, T, Takahashi, A, Matsumoto, M, Herring, JA, Lam, TP, Wang, X, Tam, EMS, Song, YQ, Fan, YH, Chan, D, Cheah, KSE, Qiu, X, Jiang, H, Huang, D, Su, P, Sham, P, Cheung, KMC, Luk, KDK, Gordon, D, Qiu, Y, Cheng, J, Tang, N, Ikegawa, S & Wise, CA 2014, 'A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1 locus in multiple ethnic groups', Journal of Medical Genetics, vol. 51, no. 6, pp. 401-406. https://doi.org/10.1136/jmedgenet-2013-102067
Londono, Douglas ; Kou, Ikuyo ; Johnson, Todd A. ; Sharma, Swarkar ; Ogura, Yoji ; Tsunoda, Tatsuhiko ; Takahashi, Atsushi ; Matsumoto, Morio ; Herring, John A. ; Lam, Tsz Ping ; Wang, Xingyan ; Tam, Elisa M S ; Song, You Qiang ; Fan, Yan Hui ; Chan, Danny ; Cheah, Kathryn S E ; Qiu, Xusheng ; Jiang, Hua ; Huang, Dongsheng ; Su, Peiqiang ; Sham, Pak ; Cheung, Kenneth M C ; Luk, Keith D K ; Gordon, Derek ; Qiu, Yong ; Cheng, Jack ; Tang, Nelson ; Ikegawa, Shiro ; Wise, Carol A. / A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1 locus in multiple ethnic groups. In: Journal of Medical Genetics. 2014 ; Vol. 51, No. 6. pp. 401-406.
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abstract = "Background: Adolescent idiopathic scoliosis (AIS) is a common rotational deformity of the spine that presents in children worldwide, yet its etiology is poorly understood. Recent genome-wide association studies (GWAS) have identified a few candidate risk loci. One locus near the chromosome 10q24.31 LBX1 gene (OMIM #604255) was originally identified by a GWAS of Japanese subjects and replicated in additional Asian populations. To extend this result, and to create larger AIS cohorts for the purpose of large-scale meta-analyses in multiple ethnicities, we formed a collaborative group called the International Consortium for Scoliosis Genetics (ICSG). Methods: Here, we report the first ICSG study, a metaanalysis of the LBX1 locus in six Asian and three non- Asian cohorts. Results: We find significant evidence for association of this locus with AIS susceptibility in all nine cohorts. Results for seven cohorts containing both genders yielded P=1.22-10-43 for rs11190870, and P=2.94-10-48 for females in all nine cohorts. Comparing the regional haplotype structures for three populations, we refined the boundaries of association to a ̃25 kb block encompassing the LBX1 gene. The LBX1 protein, a homeobox transcription factor that is orthologous to the Drosophila ladybird late gene, is involved in proper migration of muscle precursor cells, specification of cardiac neural crest cells, and neuronal determination in developing neural tubes. Conclusions: Our results firmly establish the LBX1 region as the first major susceptibility locus for AIS in Asian and non-Hispanic white groups, and provide a platform for larger studies in additional ancestral groups.",
author = "Douglas Londono and Ikuyo Kou and Johnson, {Todd A.} and Swarkar Sharma and Yoji Ogura and Tatsuhiko Tsunoda and Atsushi Takahashi and Morio Matsumoto and Herring, {John A.} and Lam, {Tsz Ping} and Xingyan Wang and Tam, {Elisa M S} and Song, {You Qiang} and Fan, {Yan Hui} and Danny Chan and Cheah, {Kathryn S E} and Xusheng Qiu and Hua Jiang and Dongsheng Huang and Peiqiang Su and Pak Sham and Cheung, {Kenneth M C} and Luk, {Keith D K} and Derek Gordon and Yong Qiu and Jack Cheng and Nelson Tang and Shiro Ikegawa and Wise, {Carol A.}",
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TY - JOUR

T1 - A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1 locus in multiple ethnic groups

AU - Londono, Douglas

AU - Kou, Ikuyo

AU - Johnson, Todd A.

AU - Sharma, Swarkar

AU - Ogura, Yoji

AU - Tsunoda, Tatsuhiko

AU - Takahashi, Atsushi

AU - Matsumoto, Morio

AU - Herring, John A.

AU - Lam, Tsz Ping

AU - Wang, Xingyan

AU - Tam, Elisa M S

AU - Song, You Qiang

AU - Fan, Yan Hui

AU - Chan, Danny

AU - Cheah, Kathryn S E

AU - Qiu, Xusheng

AU - Jiang, Hua

AU - Huang, Dongsheng

AU - Su, Peiqiang

AU - Sham, Pak

AU - Cheung, Kenneth M C

AU - Luk, Keith D K

AU - Gordon, Derek

AU - Qiu, Yong

AU - Cheng, Jack

AU - Tang, Nelson

AU - Ikegawa, Shiro

AU - Wise, Carol A.

PY - 2014

Y1 - 2014

N2 - Background: Adolescent idiopathic scoliosis (AIS) is a common rotational deformity of the spine that presents in children worldwide, yet its etiology is poorly understood. Recent genome-wide association studies (GWAS) have identified a few candidate risk loci. One locus near the chromosome 10q24.31 LBX1 gene (OMIM #604255) was originally identified by a GWAS of Japanese subjects and replicated in additional Asian populations. To extend this result, and to create larger AIS cohorts for the purpose of large-scale meta-analyses in multiple ethnicities, we formed a collaborative group called the International Consortium for Scoliosis Genetics (ICSG). Methods: Here, we report the first ICSG study, a metaanalysis of the LBX1 locus in six Asian and three non- Asian cohorts. Results: We find significant evidence for association of this locus with AIS susceptibility in all nine cohorts. Results for seven cohorts containing both genders yielded P=1.22-10-43 for rs11190870, and P=2.94-10-48 for females in all nine cohorts. Comparing the regional haplotype structures for three populations, we refined the boundaries of association to a ̃25 kb block encompassing the LBX1 gene. The LBX1 protein, a homeobox transcription factor that is orthologous to the Drosophila ladybird late gene, is involved in proper migration of muscle precursor cells, specification of cardiac neural crest cells, and neuronal determination in developing neural tubes. Conclusions: Our results firmly establish the LBX1 region as the first major susceptibility locus for AIS in Asian and non-Hispanic white groups, and provide a platform for larger studies in additional ancestral groups.

AB - Background: Adolescent idiopathic scoliosis (AIS) is a common rotational deformity of the spine that presents in children worldwide, yet its etiology is poorly understood. Recent genome-wide association studies (GWAS) have identified a few candidate risk loci. One locus near the chromosome 10q24.31 LBX1 gene (OMIM #604255) was originally identified by a GWAS of Japanese subjects and replicated in additional Asian populations. To extend this result, and to create larger AIS cohorts for the purpose of large-scale meta-analyses in multiple ethnicities, we formed a collaborative group called the International Consortium for Scoliosis Genetics (ICSG). Methods: Here, we report the first ICSG study, a metaanalysis of the LBX1 locus in six Asian and three non- Asian cohorts. Results: We find significant evidence for association of this locus with AIS susceptibility in all nine cohorts. Results for seven cohorts containing both genders yielded P=1.22-10-43 for rs11190870, and P=2.94-10-48 for females in all nine cohorts. Comparing the regional haplotype structures for three populations, we refined the boundaries of association to a ̃25 kb block encompassing the LBX1 gene. The LBX1 protein, a homeobox transcription factor that is orthologous to the Drosophila ladybird late gene, is involved in proper migration of muscle precursor cells, specification of cardiac neural crest cells, and neuronal determination in developing neural tubes. Conclusions: Our results firmly establish the LBX1 region as the first major susceptibility locus for AIS in Asian and non-Hispanic white groups, and provide a platform for larger studies in additional ancestral groups.

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