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Fine-Mapping Array Design for Multi-Ethnic Studies of Multiple Sclerosis

1
John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
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John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
*
Author to whom correspondence should be addressed.
Genes 2019, 10(11), 903; https://doi.org/10.3390/genes10110903
Received: 30 September 2019 / Revised: 31 October 2019 / Accepted: 5 November 2019 / Published: 7 November 2019
While approximately 200 autosomal genetic associations outside of the major histocompatibility complex (MHC) have been identified for multiple sclerosis (MS) risk in European populations, causal variants identified at the majority of these associated loci have been much more elusive. We propose that knowledge gained from replication efforts in Hispanic and African American populations can be utilized to more efficiently fine-map these risk loci. To this end, we have customized a genotyping array by adding ~20,000 bead types (~17,000 variants) to the base content of the Ilumina Infinium expanded multi-ethnic genotyping array and the Infinium ImmunoArray-24 v2 BeadChip. These custom bead types were chosen to allow for the detection of causal variation (1) in the presence of allelic and locus heterogeneity, by incorporating regulatory and coding variation within 1-Mb of previously identified risk variants and (2) in the absence of allelic and locus heterogeneity by incorporation of variants using linkage disequilibrium criteria, which are based on knowledge of replication status in Hispanic and African American study samples. This array has been designed to maximize fine-mapping potential for currently identified MS susceptibility loci, particularly in multi-ethnic populations. The strategies described here could be additionally informative for fine-mapping of other disease phenotypes. View Full-Text
Keywords: multiple sclerosis; fine-mapping; association multiple sclerosis; fine-mapping; association
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Beecham, A.H.; McCauley, J.L. Fine-Mapping Array Design for Multi-Ethnic Studies of Multiple Sclerosis. Genes 2019, 10, 903.

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