Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium

Qiao Fan, Xiaobo Guo, J. Willem L Tideman, Katie M. Williams, Seyhan Yazar, S. Mohsen Hosseini, Laura D. Howe, Beaté St Pourcain, David M. Evans, Nicholas J. Timpson, George McMahon, Pirro G. Hysi, Eva Krapohl, Ya Xing Wang, Jost B. Jonas, Paul Nigel Baird, Jie Jin Wang, Ching Yu Cheng, Yik Ying Teo, Tien Yin Wong & 31 others Xiaohu Ding, Robert Wojciechowski, Terri L. Young, Olavi Pärssinen, Konrad Oexle, Norbert Pfeiffer, Joan E. Bailey-Wilson, Andrew D. Paterson, Caroline C W Klaver, Robert Plomin, Christopher J. Hammond, Mingguang He, Seang Mei Saw, Jeremy A. Guggenheim, Akira Meguro, Alan F. Wright, Alex W. Hewitt, Alvin L. Young, Amutha Barathi Veluchamy, Andres Metspalu, Angela Döring, Anthony P. Khawaja, Barbara E. Klein, Beate St Pourcain, Brian Fleck, Caroline C W Klaver, Caroline Hayward, Cathy Williams, Cécile Delcourt, Rhys D. Fogarty, The CREAM Consortium

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Abstract

Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).

LanguageEnglish
Article number25853
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 13 May 2016

ASJC Scopus subject areas

  • General

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Fan, Qiao ; Guo, Xiaobo ; Tideman, J. Willem L ; Williams, Katie M. ; Yazar, Seyhan ; Hosseini, S. Mohsen ; Howe, Laura D. ; Pourcain, Beaté St ; Evans, David M. ; Timpson, Nicholas J. ; McMahon, George ; Hysi, Pirro G. ; Krapohl, Eva ; Wang, Ya Xing ; Jonas, Jost B. ; Baird, Paul Nigel ; Wang, Jie Jin ; Cheng, Ching Yu ; Teo, Yik Ying ; Wong, Tien Yin ; Ding, Xiaohu ; Wojciechowski, Robert ; Young, Terri L. ; Pärssinen, Olavi ; Oexle, Konrad ; Pfeiffer, Norbert ; Bailey-Wilson, Joan E. ; Paterson, Andrew D. ; Klaver, Caroline C W ; Plomin, Robert ; Hammond, Christopher J. ; He, Mingguang ; Saw, Seang Mei ; Guggenheim, Jeremy A. ; Meguro, Akira ; Wright, Alan F. ; Hewitt, Alex W. ; Young, Alvin L. ; Veluchamy, Amutha Barathi ; Metspalu, Andres ; Döring, Angela ; Khawaja, Anthony P. ; Klein, Barbara E. ; St Pourcain, Beate ; Fleck, Brian ; Klaver, Caroline C W ; Hayward, Caroline ; Williams, Cathy ; Delcourt, Cécile ; Fogarty, Rhys D. ; The CREAM Consortium. / Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia : The CREAM Consortium. In: Scientific Reports. 2016 ; Vol. 6.
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title = "Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium",
abstract = "Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6{\%} (P = 6.6E-08) and 2.3{\%} (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).",
author = "Qiao Fan and Xiaobo Guo and Tideman, {J. Willem L} and Williams, {Katie M.} and Seyhan Yazar and Hosseini, {S. Mohsen} and Howe, {Laura D.} and Pourcain, {Beat{\'e} St} and Evans, {David M.} and Timpson, {Nicholas J.} and George McMahon and Hysi, {Pirro G.} and Eva Krapohl and Wang, {Ya Xing} and Jonas, {Jost B.} and Baird, {Paul Nigel} and Wang, {Jie Jin} and Cheng, {Ching Yu} and Teo, {Yik Ying} and Wong, {Tien Yin} and Xiaohu Ding and Robert Wojciechowski and Young, {Terri L.} and Olavi P{\"a}rssinen and Konrad Oexle and Norbert Pfeiffer and Bailey-Wilson, {Joan E.} and Paterson, {Andrew D.} and Klaver, {Caroline C W} and Robert Plomin and Hammond, {Christopher J.} and Mingguang He and Saw, {Seang Mei} and Guggenheim, {Jeremy A.} and Akira Meguro and Wright, {Alan F.} and Hewitt, {Alex W.} and Young, {Alvin L.} and Veluchamy, {Amutha Barathi} and Andres Metspalu and Angela D{\"o}ring and Khawaja, {Anthony P.} and Klein, {Barbara E.} and {St Pourcain}, Beate and Brian Fleck and Klaver, {Caroline C W} and Caroline Hayward and Cathy Williams and C{\'e}cile Delcourt and Fogarty, {Rhys D.} and {The CREAM Consortium}",
year = "2016",
month = "5",
day = "13",
doi = "10.1038/srep25853",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

Fan, Q, Guo, X, Tideman, JWL, Williams, KM, Yazar, S, Hosseini, SM, Howe, LD, Pourcain, BS, Evans, DM, Timpson, NJ, McMahon, G, Hysi, PG, Krapohl, E, Wang, YX, Jonas, JB, Baird, PN, Wang, JJ, Cheng, CY, Teo, YY, Wong, TY, Ding, X, Wojciechowski, R, Young, TL, Pärssinen, O, Oexle, K, Pfeiffer, N, Bailey-Wilson, JE, Paterson, AD, Klaver, CCW, Plomin, R, Hammond, CJ, He, M, Saw, SM, Guggenheim, JA, Meguro, A, Wright, AF, Hewitt, AW, Young, AL, Veluchamy, AB, Metspalu, A, Döring, A, Khawaja, AP, Klein, BE, St Pourcain, B, Fleck, B, Klaver, CCW, Hayward, C, Williams, C, Delcourt, C, Fogarty, RD & The CREAM Consortium 2016, 'Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium', Scientific Reports, vol. 6, 25853. https://doi.org/10.1038/srep25853

Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia : The CREAM Consortium. / Fan, Qiao; Guo, Xiaobo; Tideman, J. Willem L; Williams, Katie M.; Yazar, Seyhan; Hosseini, S. Mohsen; Howe, Laura D.; Pourcain, Beaté St; Evans, David M.; Timpson, Nicholas J.; McMahon, George; Hysi, Pirro G.; Krapohl, Eva; Wang, Ya Xing; Jonas, Jost B.; Baird, Paul Nigel; Wang, Jie Jin; Cheng, Ching Yu; Teo, Yik Ying; Wong, Tien Yin; Ding, Xiaohu; Wojciechowski, Robert; Young, Terri L.; Pärssinen, Olavi; Oexle, Konrad; Pfeiffer, Norbert; Bailey-Wilson, Joan E.; Paterson, Andrew D.; Klaver, Caroline C W; Plomin, Robert; Hammond, Christopher J.; He, Mingguang; Saw, Seang Mei; Guggenheim, Jeremy A.; Meguro, Akira; Wright, Alan F.; Hewitt, Alex W.; Young, Alvin L.; Veluchamy, Amutha Barathi; Metspalu, Andres; Döring, Angela; Khawaja, Anthony P.; Klein, Barbara E.; St Pourcain, Beate; Fleck, Brian; Klaver, Caroline C W; Hayward, Caroline; Williams, Cathy; Delcourt, Cécile; Fogarty, Rhys D.; The CREAM Consortium.

In: Scientific Reports, Vol. 6, 25853, 13.05.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia

T2 - Scientific Reports

AU - Fan, Qiao

AU - Guo, Xiaobo

AU - Tideman, J. Willem L

AU - Williams, Katie M.

AU - Yazar, Seyhan

AU - Hosseini, S. Mohsen

AU - Howe, Laura D.

AU - Pourcain, Beaté St

AU - Evans, David M.

AU - Timpson, Nicholas J.

AU - McMahon, George

AU - Hysi, Pirro G.

AU - Krapohl, Eva

AU - Wang, Ya Xing

AU - Jonas, Jost B.

AU - Baird, Paul Nigel

AU - Wang, Jie Jin

AU - Cheng, Ching Yu

AU - Teo, Yik Ying

AU - Wong, Tien Yin

AU - Ding, Xiaohu

AU - Wojciechowski, Robert

AU - Young, Terri L.

AU - Pärssinen, Olavi

AU - Oexle, Konrad

AU - Pfeiffer, Norbert

AU - Bailey-Wilson, Joan E.

AU - Paterson, Andrew D.

AU - Klaver, Caroline C W

AU - Plomin, Robert

AU - Hammond, Christopher J.

AU - He, Mingguang

AU - Saw, Seang Mei

AU - Guggenheim, Jeremy A.

AU - Meguro, Akira

AU - Wright, Alan F.

AU - Hewitt, Alex W.

AU - Young, Alvin L.

AU - Veluchamy, Amutha Barathi

AU - Metspalu, Andres

AU - Döring, Angela

AU - Khawaja, Anthony P.

AU - Klein, Barbara E.

AU - St Pourcain, Beate

AU - Fleck, Brian

AU - Klaver, Caroline C W

AU - Hayward, Caroline

AU - Williams, Cathy

AU - Delcourt, Cécile

AU - Fogarty, Rhys D.

AU - The CREAM Consortium

PY - 2016/5/13

Y1 - 2016/5/13

N2 - Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).

AB - Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).

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U2 - 10.1038/srep25853

DO - 10.1038/srep25853

M3 - Article

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

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