Homozygosity Analysis in Autoimmunity Affected Individuals and Multiplex Autoimmune Disease Families

John Castiblanco, Juan Manuel Anaya

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Autoimmune diseases (AD) are responsible for a substantial amount of disability and morbidity worldwide. Research generally focuses on a single disease, although autoimmune phenotypes could represent pleiotropic outcomes of non-specific disease genes underlying similar immunogenetic mechanisms. This report examined the effect and importance of the homozygosity status, using genome-wide interspersed markers, in individuals and multiplex families affected with AD. This study presented two approaches: (I) a case-control comparison and evaluation on the effect of homozygosity at the genome-wide level and per marker, including 453 unrelated individuals (121 late-, 79 early-onset AD, 40 polyautoimmunity (PolyA), 30 multiple autoimmune syndrome (MAS) and 183 healthy control individuals); and (II) a model-free affected pair linkage approach which included 35 MAS, 49 polyA, 104 late-, and 83 early-onset multiplex families. A total of 372 genome-wide markers were used in the analysis. The tandardized observed homozygosity (SOH) was calculated and the association of the homozygosity status and the autoimmune trait was evaluated. The multipoint model-free linkage analysis was applied by using

RELPAL from S.A.G.E v6.3. Results for the SOH showed significant differences between controls and early-onset individuals, where early-onset affected individuals showed lower homozygosity relative to controls. No differences were observed relative to controls for MAS, polyA and late-onset disease at the genome-wide level. The local marker homozygosity effect showed share and specific risk and/or protective effects for 24 markers. The model-free affected pair linkage approach lacked any suggestive linkage signals, but marginal signals displayed excess allele
sharing for extreme phenotypes in autoimmunity. This study presumed autoimmunity as a trait rather than a clinical phenotype and tried to approach AD as a continuous trait presenting extreme phenotypes. Future approaches would be expected to dwell on the data presented here to corroborate and expand on sample size, marker coverage and their effects.
Translated title of the contributionAnálisis de homocigosidad en individuos afectados por la autoinmunidad y en familias con enfermedades autoinmunes múltiples
Original languageEnglish
Article number1000136
JournalImmunome Research
Issue number3
StatePublished - Jul 7 2017

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