TY - JOUR
T1 - Family-based genome-wide association study of south Indian pedigrees supports WNT7B as a central corneal thickness locus
AU - Fan, Bao Jian
AU - Chen, Xueli
AU - Sondhi, Nisha
AU - Sharmila, P. Ferdinamarie
AU - Soumittra, Nagasamy
AU - Sripriya, Sarangapani
AU - Sacikala, Srinivasan
AU - Asokan, Rashima
AU - Friedman, David S.
AU - Pasquale, Louis R.
AU - Gao, X. Raymond
AU - Vijaya, Lingam
AU - Bailey, Jessica Cooke
AU - Vitart, Veronique
AU - Macgregor, Stuart
AU - Hammond, Christopher J.
AU - Khor, Chiea Chuen
AU - Haines, Jonathan L.
AU - George, Ronnie
AU - Wiggs, Janey L.
AU - Mexican American Glaucoma Genetic Study
AU - Allingham, R. Rand
AU - Gao, X. Raymond
AU - Gauderman, Jim
AU - Hauser, Michael
AU - Rotter, Jerome I.
AU - Varma, Rohit
AU - Wiggs, Janey
AU - International Glaucoma Genetics Consortium
AU - Aung, Tin
AU - Burdon, Kathryn P.
AU - Cheng, Ching Yu
AU - Craig, Jamie E.
AU - Cree, Angela J.
AU - Gharahkhani, Puya
AU - Hammond, Christopher J.
AU - Hewitt, Alex W.
AU - Höhn, René
AU - Hysi, Pirro
AU - Iglesias Gonzalez, Adriana I.
AU - Jonas, Jost
AU - Khawaja, Anthony
AU - Khor, Chiea Cheun
AU - Klaver, Caroline C.W.
AU - Pasutto, Francesca
AU - McGregor, Stuart
AU - Mackey, David
AU - Mitchell, Paul
AU - Mishra, Aniket
AU - Pang, Calvin
AU - Pasquale, Louis R.
AU - Pasutto, Francesca
AU - Springelkamp, Henriette
AU - Thorleifsson, Gudmar
AU - Thorsteinsdottir, Unnur
AU - van Duijn, Cornelia M.
AU - Viswanathan, Ananth
AU - Vitart, Veronique
AU - Wiggs, Janey L.
AU - Wojciechowski, Robert
AU - Wong, Tien
AU - Young, Terri L.
AU - Zeller, Tanja
AU - NEIGHBORHOOD Consortium
AU - Allingham, Rand
AU - Brilliant, Murray
AU - Budenz, Don
AU - Bailey, Jessica Cooke
AU - Fingert, John
AU - Gaasterland, Douglas
AU - Gaasterland, Teresa
AU - Haines, Jonathan L.
AU - Hauser, Michael
AU - Igo, Rob
AU - Kang, Jae Hee
AU - Kraft, Peter
AU - Lee, Richard
AU - Lichter, Paul
AU - Liu, Yutao
AU - Moroi, Syoko
AU - Pasquale, Louis R.
AU - Realini, Anthony
AU - Rhee, Doug
AU - Richards, Julia R.
AU - Ritch, Robert
AU - Schuman, Joel
AU - Scott, William K.
AU - Singh, Kuldev
AU - Sit, Arthur
AU - Vollrath, Douglas
AU - Weinreb, Robert N.
AU - Wiggs, Janey L.
AU - Wollstein, Gadi
AU - Zack, Don
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Purpose: To identify genetic risk factors contributing to central corneal thickness (CCT) in individuals from South India, a population with a high prevalence of ocular disorders. Methods: One hundred ninety-five individuals from 15 large South Indian pedigrees were genotyped using the Omni2.5 bead array. Family-based association for CCT was conducted using the score test in MERLIN. Results: Genome-wide association study (GWAS) identified strongest association for single nucleotide polymorphisms (SNPs) in the first intron of WNT7B and CCT (top SNP rs9330813; β = −0.57, 95% confidence interval CI: −0.78 to −0.36; P = 1.7 × 10−7). We further investigated rs9330813 in a Latino cohort and four independent European cohorts. A meta-analysis of these data sets demonstrated statistically significant association between rs9330813 and CCT (β = −3.94, 95% CI: −5.23 to −2.66; P = 1.7 × 10−9). WNT7B SNPs located in the same genomic region that includes rs9330813 have previously been associated with CCT in Latinos but with other ocular quantitative traits related to myopia (corneal curvature and axial length) in a Japanese population (rs10453441 and rs200329677). To evaluate the specificity of the observed WNT7B association with CCT in the South Indian families, we completed an ocular phenome-wide association study (PheWAS) for the top WNT7B SNPs using 45 ocular traits measured in these same families including corneal curvature and axial length. The ocular PheWAS results indicate that in the South Indian families WNT7B SNPs are primarily associated with CCT. Conclusions: The results indicate robust evidence for association between WNT7B SNPs and CCT in South Indian pedigrees, and suggest that WNT7B SNPs can have population-specific effects on ocular quantitative traits.
AB - Purpose: To identify genetic risk factors contributing to central corneal thickness (CCT) in individuals from South India, a population with a high prevalence of ocular disorders. Methods: One hundred ninety-five individuals from 15 large South Indian pedigrees were genotyped using the Omni2.5 bead array. Family-based association for CCT was conducted using the score test in MERLIN. Results: Genome-wide association study (GWAS) identified strongest association for single nucleotide polymorphisms (SNPs) in the first intron of WNT7B and CCT (top SNP rs9330813; β = −0.57, 95% confidence interval CI: −0.78 to −0.36; P = 1.7 × 10−7). We further investigated rs9330813 in a Latino cohort and four independent European cohorts. A meta-analysis of these data sets demonstrated statistically significant association between rs9330813 and CCT (β = −3.94, 95% CI: −5.23 to −2.66; P = 1.7 × 10−9). WNT7B SNPs located in the same genomic region that includes rs9330813 have previously been associated with CCT in Latinos but with other ocular quantitative traits related to myopia (corneal curvature and axial length) in a Japanese population (rs10453441 and rs200329677). To evaluate the specificity of the observed WNT7B association with CCT in the South Indian families, we completed an ocular phenome-wide association study (PheWAS) for the top WNT7B SNPs using 45 ocular traits measured in these same families including corneal curvature and axial length. The ocular PheWAS results indicate that in the South Indian families WNT7B SNPs are primarily associated with CCT. Conclusions: The results indicate robust evidence for association between WNT7B SNPs and CCT in South Indian pedigrees, and suggest that WNT7B SNPs can have population-specific effects on ocular quantitative traits.
KW - Cornea central thickness
KW - Genetic association
KW - Ocular PheWAS
KW - Quantitative trait
KW - WNT7B
UR - http://www.scopus.com/inward/record.url?scp=85047451548&partnerID=8YFLogxK
U2 - 10.1167/iovs.17-23536
DO - 10.1167/iovs.17-23536
M3 - Article
C2 - 29847655
AN - SCOPUS:85047451548
VL - 59
SP - 2495
EP - 2502
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 1552-5783
IS - 6
ER -