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Baojian Fan, P. Ferdina Marie Sharmila, N. Soumittra, S. Sripriya, David S Friedman, L. Vijaya, Jonathan L Haines, Ronnie J George, Janey L Wiggs; Genome-wide Linkage Analysis Using Large Consanguineous Pedigrees from South India Identifies New Loci for Ocular Quantitative Traits. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6406. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Many ocular quantitative traits are highly heritable. Mapping genes contributing to these quantitative traits may effectively identify genetic risk factors predisposing to related complex diseases, such as glaucoma. Compared to outbred pedigrees, consanguineous pedigrees are expected to have more power to identify quantitative trait alleles with additive or subtractive effects. Additionally, inbreeding due to social customs or geographic constraints may reduce genetic heterogeneity. The purpose of this study is to use consanguineous pedigrees from South India for mapping genetic loci for ocular quantitative traits.
240 members of 16 Indian consanguineous pedigrees from South India (Chennai) underwent a comprehensive ophthalmic examination for 49 selected ocular quantitative traits. Genotyping was performed using the Illumina HumanOmni2.5-8 platform. Multipoint linkage analysis of 1,223,314 SNPs was performed using the variance components analysis in MERLIN (v1.1.2). All traits were adjusted for age and sex, and inverse-normal transformation of ranks was applied before analysis.
Significant novel linkage signals (LOD > 3.3) were identified for astigmatic refractive error (LOD = 6.58 on 14q21.3-22.1, 5.68 on 16p12.3, 4.62 on 13q31.3 and 4.44 on 10p15.3), cup depth (LOD = 3.92 on 12q24.31), vertical cup-disc ratio (LOD = 3.62 on 14q32.12), lens thickness (LOD = 3.50 on 3p22.3) and axial length (LOD = 3.45 on 6q24.1). Suggestive evidence of linkage (LOD > 1.9) was identified for anterior chamber depth, central corneal thickness, contour line modulation temporal to inferior, corneal resistance factor, cup disc area ratio, cup size, cup volume, horizontal cup disc ratio, linear cup disc ratio, maximum contour depression, reference height, rim area, rim disc area ratio, rim steepness, rim volume, temporal superior nasal inferior temporal average and waveform score.
This study shows that a relatively small number of consanguineous pedigrees can provide sufficient power to identify quantitative trait loci. Further evaluation of interesting candidate genes located within these linkage intervals is ongoing.
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