Genome-wide association identifies novel ROP risk loci in a multiethnic cohort

Xiaohui Li; Leah A. Owen; Kent D. Taylor; Susan Ostmo; Yii Der Ida Chen; Aaron S. Coyner; Kemal Sonmez; M. Elizabeth Hartnett; Xiuqing Guo; Eli Ipp; Kathryn Roll; Pauline Genter; R. V.Paul Chan; Margaret M. DeAngelis; Michael F. Chiang; J. Peter Campbell; Jerome I. Rotter; Susan Ostmo; Aaron Coyner; Benjamin K. Young; Sang Jin Kim; Kemal Sonmez; Robert Schelonka; Michael F. Chiang; R. V.Paul Chan; Karyn Jonas; Bhavana Kolli; Jason Horowitz; Osode Coki; Cheryl Ann Eccles; Leora Sarna; Anton Orlin; Audina Berrocal; Catherin Negron; Kimberly Denser; Kristi Cumming; Tammy Osentoski; Tammy Check; Mary Zajechowski; Thomas Lee; Aaron Nagiel; Evan Kruger; Kathryn McGovern; Dilshad Contractor; Margaret Havunjian; Charles Simmons; Raghu Murthy; Sharon Galvis; Jerome Rotter; Ida Chen; Xiaohui Li; Kent Taylor; Kaye Roll; Leah Owen; Lucia Lucci; Mary Elizabeth Hartnett; Darius Moshfeghi; Mariana Nunez; Zac Weinberg-Smith; Jayashree Kalpathy-Cramer; Deniz Erdogmus; Stratis Ioannidis; Maria Ana Martinez-Castellanos; Samantha SalinasLongoria; Rafael Romero; Andrea Arriola; Francisco Olguin-Manriquez; Miroslava Meraz-Gutierrez; Carlos M. Dulanto-Reinoso; Cristina Montero-Mendoza

doi:10.1038/s42003-023-05743-9

Genome-wide association identifies novel ROP risk loci in a multiethnic cohort

Xiaohui Li, Leah A. Owen, Kent D. Taylor, Susan Ostmo, Yii Der Ida Chen, Aaron S. Coyner, Kemal Sonmez, M. Elizabeth Hartnett, Xiuqing Guo, Eli Ipp, Kathryn Roll, Pauline Genter, R. V.Paul Chan, Margaret M. DeAngelis, Michael F. Chiang, J. Peter Campbell, Jerome I. Rotter, Susan Ostmo, Aaron Coyner, Benjamin K. YoungSang Jin Kim, Kemal Sonmez, Robert Schelonka, Michael F. Chiang, R. V.Paul Chan, Karyn Jonas, Bhavana Kolli, Jason Horowitz, Osode Coki, Cheryl Ann Eccles, Leora Sarna, Anton Orlin, Audina Berrocal, Catherin Negron, Kimberly Denser, Kristi Cumming, Tammy Osentoski, Tammy Check, Mary Zajechowski, Thomas Lee, Aaron Nagiel, Evan Kruger, Kathryn McGovern, Dilshad Contractor, Margaret Havunjian, Charles Simmons, Raghu Murthy, Sharon Galvis, Jerome Rotter, Ida Chen, Xiaohui Li, Kent Taylor, Kaye Roll, Leah Owen, Lucia Lucci, Mary Elizabeth Hartnett, Darius Moshfeghi, Mariana Nunez, Zac Weinberg-Smith, Jayashree Kalpathy-Cramer, Deniz Erdogmus, Stratis Ioannidis, Maria Ana Martinez-Castellanos, Samantha SalinasLongoria, Rafael Romero, Andrea Arriola, Francisco Olguin-Manriquez, Miroslava Meraz-Gutierrez, Carlos M. Dulanto-Reinoso, Cristina Montero-Mendoza

Research output: Contribution to journal › Article › peer-review

Abstract

We conducted a genome-wide association study (GWAS) in a multiethnic cohort of 920 at-risk infants for retinopathy of prematurity (ROP), a major cause of childhood blindness, identifying 1 locus at genome-wide significance level (p < 5×10^-8) and 9 with significance of p < 5×10^-6 for ROP ≥ stage 3. The most significant locus, rs2058019, reached genome-wide significance within the full multiethnic cohort (p = 4.96×10^-9); Hispanic and European Ancestry infants driving the association. The lead single nucleotide polymorphism (SNP) falls in an intronic region within the Glioma-associated oncogene family zinc finger 3 (GLI3) gene. Relevance for GLI3 and other top-associated genes to human ocular disease was substantiated through in-silico extension analyses, genetic risk score analysis and expression profiling in human donor eye tissues. Thus, we identify a novel locus at GLI3 with relevance to retinal biology, supporting genetic susceptibilities for ROP risk with possible variability by race and ethnicity.

Original language	English (US)
Article number	107
Journal	Communications Biology
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s42003-023-05743-9
State	Published - Dec 2024

ASJC Scopus subject areas

Medicine (miscellaneous)
General Biochemistry, Genetics and Molecular Biology
General Agricultural and Biological Sciences

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10.1038/s42003-023-05743-9

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Li, X., Owen, L. A., Taylor, K. D., Ostmo, S., Chen, Y. D. I., Coyner, A. S., Sonmez, K., Hartnett, M. E., Guo, X., Ipp, E., Roll, K., Genter, P., Chan, R. V. P., DeAngelis, M. M., Chiang, M. F., Campbell, J. P., Rotter, J. I., Ostmo, S., Coyner, A., ... Montero-Mendoza, C. (2024). Genome-wide association identifies novel ROP risk loci in a multiethnic cohort. Communications Biology, 7(1), Article 107. https://doi.org/10.1038/s42003-023-05743-9

Li, X, Owen, LA, Taylor, KD, Ostmo, S, Chen, YDI, Coyner, AS, Sonmez, K, Hartnett, ME, Guo, X, Ipp, E, Roll, K, Genter, P, Chan, RVP, DeAngelis, MM, Chiang, MF, Campbell, JP, Rotter, JI, Ostmo, S, Coyner, A, Young, BK, Kim, SJ, Sonmez, K, Schelonka, R, Chiang, MF, Chan, RVP, Jonas, K, Kolli, B, Horowitz, J, Coki, O, Eccles, CA, Sarna, L, Orlin, A, Berrocal, A, Negron, C, Denser, K, Cumming, K, Osentoski, T, Check, T, Zajechowski, M, Lee, T, Nagiel, A, Kruger, E, McGovern, K, Contractor, D, Havunjian, M, Simmons, C, Murthy, R, Galvis, S, Rotter, J, Chen, I, Li, X, Taylor, K, Roll, K, Owen, L, Lucci, L, Hartnett, ME, Moshfeghi, D, Nunez, M, Weinberg-Smith, Z, Kalpathy-Cramer, J, Erdogmus, D, Ioannidis, S, Martinez-Castellanos, MA, SalinasLongoria, S, Romero, R, Arriola, A, Olguin-Manriquez, F, Meraz-Gutierrez, M, Dulanto-Reinoso, CM & Montero-Mendoza, C 2024, 'Genome-wide association identifies novel ROP risk loci in a multiethnic cohort', Communications Biology, vol. 7, no. 1, 107. https://doi.org/10.1038/s42003-023-05743-9

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title = "Genome-wide association identifies novel ROP risk loci in a multiethnic cohort",

abstract = "We conducted a genome-wide association study (GWAS) in a multiethnic cohort of 920 at-risk infants for retinopathy of prematurity (ROP), a major cause of childhood blindness, identifying 1 locus at genome-wide significance level (p < 5×10-8) and 9 with significance of p < 5×10-6 for ROP ≥ stage 3. The most significant locus, rs2058019, reached genome-wide significance within the full multiethnic cohort (p = 4.96×10-9); Hispanic and European Ancestry infants driving the association. The lead single nucleotide polymorphism (SNP) falls in an intronic region within the Glioma-associated oncogene family zinc finger 3 (GLI3) gene. Relevance for GLI3 and other top-associated genes to human ocular disease was substantiated through in-silico extension analyses, genetic risk score analysis and expression profiling in human donor eye tissues. Thus, we identify a novel locus at GLI3 with relevance to retinal biology, supporting genetic susceptibilities for ROP risk with possible variability by race and ethnicity.",

author = "Xiaohui Li and Owen, {Leah A.} and Taylor, {Kent D.} and Susan Ostmo and Chen, {Yii Der Ida} and Coyner, {Aaron S.} and Kemal Sonmez and Hartnett, {M. Elizabeth} and Xiuqing Guo and Eli Ipp and Kathryn Roll and Pauline Genter and Chan, {R. V.Paul} and DeAngelis, {Margaret M.} and Chiang, {Michael F.} and Campbell, {J. Peter} and Rotter, {Jerome I.} and Susan Ostmo and Aaron Coyner and Young, {Benjamin K.} and Kim, {Sang Jin} and Kemal Sonmez and Robert Schelonka and Chiang, {Michael F.} and Chan, {R. V.Paul} and Karyn Jonas and Bhavana Kolli and Jason Horowitz and Osode Coki and Eccles, {Cheryl Ann} and Leora Sarna and Anton Orlin and Audina Berrocal and Catherin Negron and Kimberly Denser and Kristi Cumming and Tammy Osentoski and Tammy Check and Mary Zajechowski and Thomas Lee and Aaron Nagiel and Evan Kruger and Kathryn McGovern and Dilshad Contractor and Margaret Havunjian and Charles Simmons and Raghu Murthy and Sharon Galvis and Jerome Rotter and Ida Chen and Xiaohui Li and Kent Taylor and Kaye Roll and Leah Owen and Lucia Lucci and Hartnett, {Mary Elizabeth} and Darius Moshfeghi and Mariana Nunez and Zac Weinberg-Smith and Jayashree Kalpathy-Cramer and Deniz Erdogmus and Stratis Ioannidis and Martinez-Castellanos, {Maria Ana} and Samantha SalinasLongoria and Rafael Romero and Andrea Arriola and Francisco Olguin-Manriquez and Miroslava Meraz-Gutierrez and Dulanto-Reinoso, {Carlos M.} and Cristina Montero-Mendoza",

note = "Publisher Copyright: {\textcopyright} 2024, The Author(s).",

year = "2024",

month = dec,

doi = "10.1038/s42003-023-05743-9",

language = "English (US)",

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T1 - Genome-wide association identifies novel ROP risk loci in a multiethnic cohort

AU - Li, Xiaohui

AU - Owen, Leah A.

AU - Taylor, Kent D.

AU - Ostmo, Susan

AU - Chen, Yii Der Ida

AU - Coyner, Aaron S.

AU - Sonmez, Kemal

AU - Hartnett, M. Elizabeth

AU - Guo, Xiuqing

AU - Ipp, Eli

AU - Roll, Kathryn

AU - Genter, Pauline

AU - Chan, R. V.Paul

AU - DeAngelis, Margaret M.

AU - Chiang, Michael F.

AU - Campbell, J. Peter

AU - Rotter, Jerome I.

AU - Ostmo, Susan

AU - Coyner, Aaron

AU - Young, Benjamin K.

AU - Kim, Sang Jin

AU - Sonmez, Kemal

AU - Schelonka, Robert

AU - Chiang, Michael F.

AU - Chan, R. V.Paul

AU - Jonas, Karyn

AU - Kolli, Bhavana

AU - Horowitz, Jason

AU - Coki, Osode

AU - Eccles, Cheryl Ann

AU - Sarna, Leora

AU - Orlin, Anton

AU - Berrocal, Audina

AU - Negron, Catherin

AU - Denser, Kimberly

AU - Cumming, Kristi

AU - Osentoski, Tammy

AU - Check, Tammy

AU - Zajechowski, Mary

AU - Lee, Thomas

AU - Nagiel, Aaron

AU - Kruger, Evan

AU - McGovern, Kathryn

AU - Contractor, Dilshad

AU - Havunjian, Margaret

AU - Simmons, Charles

AU - Murthy, Raghu

AU - Galvis, Sharon

AU - Rotter, Jerome

AU - Chen, Ida

AU - Li, Xiaohui

AU - Taylor, Kent

AU - Roll, Kaye

AU - Owen, Leah

AU - Lucci, Lucia

AU - Hartnett, Mary Elizabeth

AU - Moshfeghi, Darius

AU - Nunez, Mariana

AU - Weinberg-Smith, Zac

AU - Kalpathy-Cramer, Jayashree

AU - Erdogmus, Deniz

AU - Ioannidis, Stratis

AU - Martinez-Castellanos, Maria Ana

AU - SalinasLongoria, Samantha

AU - Romero, Rafael

AU - Arriola, Andrea

AU - Olguin-Manriquez, Francisco

AU - Meraz-Gutierrez, Miroslava

AU - Dulanto-Reinoso, Carlos M.

AU - Montero-Mendoza, Cristina

PY - 2024/12

Y1 - 2024/12

N2 - We conducted a genome-wide association study (GWAS) in a multiethnic cohort of 920 at-risk infants for retinopathy of prematurity (ROP), a major cause of childhood blindness, identifying 1 locus at genome-wide significance level (p < 5×10-8) and 9 with significance of p < 5×10-6 for ROP ≥ stage 3. The most significant locus, rs2058019, reached genome-wide significance within the full multiethnic cohort (p = 4.96×10-9); Hispanic and European Ancestry infants driving the association. The lead single nucleotide polymorphism (SNP) falls in an intronic region within the Glioma-associated oncogene family zinc finger 3 (GLI3) gene. Relevance for GLI3 and other top-associated genes to human ocular disease was substantiated through in-silico extension analyses, genetic risk score analysis and expression profiling in human donor eye tissues. Thus, we identify a novel locus at GLI3 with relevance to retinal biology, supporting genetic susceptibilities for ROP risk with possible variability by race and ethnicity.

AB - We conducted a genome-wide association study (GWAS) in a multiethnic cohort of 920 at-risk infants for retinopathy of prematurity (ROP), a major cause of childhood blindness, identifying 1 locus at genome-wide significance level (p < 5×10-8) and 9 with significance of p < 5×10-6 for ROP ≥ stage 3. The most significant locus, rs2058019, reached genome-wide significance within the full multiethnic cohort (p = 4.96×10-9); Hispanic and European Ancestry infants driving the association. The lead single nucleotide polymorphism (SNP) falls in an intronic region within the Glioma-associated oncogene family zinc finger 3 (GLI3) gene. Relevance for GLI3 and other top-associated genes to human ocular disease was substantiated through in-silico extension analyses, genetic risk score analysis and expression profiling in human donor eye tissues. Thus, we identify a novel locus at GLI3 with relevance to retinal biology, supporting genetic susceptibilities for ROP risk with possible variability by race and ethnicity.

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JO - Communications Biology

JF - Communications Biology

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ER -

Genome-wide association identifies novel ROP risk loci in a multiethnic cohort

Abstract

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