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

Tideman JW; Yazar S; McMahon G; Teo YY; Wang YX; Hammond CJ; Baird PN; Wang JJ; Hosseini SM; Saw SM; Plomin R; Guggenheim JA; The CREAM Consortium; Howe LD; He M; Pourcain BS; Klaver CC; Guo X; Wong TY; Pfeiffer N; Wojciechowski R; Paterson AD; Cheng CY; Fan Q; Oexle K; Williams C; Williams KM; Timpson NJ; Mackey DA; Krapohl E; Bailey-Wilson JE; Ding X; Pärssinen O; Hysi PG; Jonas JB; Evans DM; Young TL

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

Tideman JW
Yazar S
McMahon G
Teo YY
Wang YX
Hammond CJ
Baird PN
Wang JJ
Hosseini SM
Saw SM
Plomin R
Guggenheim JA; The CREAM Consortium
Howe LD
He M
Pourcain BS
Klaver CC
Guo X
Wong TY
Pfeiffer N
Wojciechowski R
Paterson AD
Cheng CY
Fan Q
Oexle K
Williams C
Williams KM
Timpson NJ
Mackey DA
Krapohl E
Bailey-Wilson JE
Ding X
Pärssinen O
Hysi PG
Jonas JB
Evans DM
Young TL
Katso/Avaa
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doi:10.1038/srep25853
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042716193
Tiivistelmä

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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