title: Single Nucleotide Polymorphism Clustering in Systemic Autoimmune Diseases.
abstract: Systemic Autoimmune Diseases, a group of chronic inflammatory conditions, have variable symptoms and difficult diagnosis. In order to reclassify them based on genetic markers rather than clinical criteria, we performed clustering of Single Nucleotide Polymorphisms. However naive approaches tend to group patients primarily by their geographic origin. To reduce this "ancestry signal", we developed SNPClust, a method to select large sources of ancestry-independent genetic variations from all variations detected by Principal Component Analysis. Applied to a Systemic Lupus Erythematosus case control dataset, SNPClust successfully reduced the ancestry signal. Results were compared with association studies between the cases and controls without or with reference population stratification correction methods. SNPClust amplified the disease discriminating signal and the ratio of significant associations outside the HLA locus was greater compared to population stratification correction methods. SNPClust will enable the use of ancestry-independent genetic information in the reclassification of Systemic Autoimmune Diseases. SNPClust is available as an R package and demonstrated on the public Human Genome Diversity Project dataset at https://github.com/ThomasChln/snpclust.
authors.affiliation: Quartz Bio, Plan-les-Ouates, Geneva, Switzerland.|Stochastic Information Processing, University of Geneva, Geneva, Geneva, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Charlon
authors.affiliation: Center for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Government, Granada, Granada, Spain.
authors.forename: Manuel
authors.identifier: http://orcid.org/0000-0002-4333-4487
authors.initials: M
authors.lastname: Martínez-Bueno
authors.affiliation: Institute of Parasitology and Biomedicine López Neyra, Spanish National Research Council, Armilla, Granada, Spain.
authors.forename: Lara
authors.initials: L
authors.lastname: Bossini-Castillo
authors.affiliation: Institute of Parasitology and Biomedicine López Neyra, Spanish National Research Council, Armilla, Granada, Spain.
authors.forename: F David
authors.initials: FD
authors.lastname: Carmona
authors.affiliation: Quartz Bio, Plan-les-Ouates, Geneva, Switzerland.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Di Cara
authors.affiliation: Quartz Bio, Plan-les-Ouates, Geneva, Switzerland.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Wojcik
authors.affiliation: Stochastic Information Processing, University of Geneva, Geneva, Geneva, Switzerland.
authors.forename: Sviatoslav
authors.initials: S
authors.lastname: Voloshynovskiy
authors.affiliation: Institute of Parasitology and Biomedicine López Neyra, Spanish National Research Council, Armilla, Granada, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
authors.affiliation: Center for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Government, Granada, Granada, Spain.
authors.forename: Marta E
authors.initials: ME
authors.lastname: Alarcón-Riquelme
mesh_terms: D030541:Databases, Genetic; D006680:HLA Antigens / Q000235:genetics*; D016045:Human Genome Project; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000145:classification / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D006680:HLA Antigens