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Genome‐Wide Association Study in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture

Overview of attention for article published in Arthritis & Rheumatology, March 2016
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Title
Genome‐Wide Association Study in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture
Published in
Arthritis & Rheumatology, March 2016
DOI 10.1002/art.39504
Pubmed ID
Authors

Marta E Alarcón-Riquelme, Julie T Ziegler, Julio Molineros, Timothy D Howard, Andrés Moreno-Estrada, Elena Sánchez-Rodríguez, Hannah C Ainsworth, Patricia Ortiz-Tello, Mary E Comeau, Astrid Rasmussen, Jennifer A Kelly, Adam Adler, Eduardo M Acevedo-Vázquez, Jorge Mariano Cucho-Venegas, Ignacio García-De la Torre, Mario H Cardiel, Pedro Miranda, Luis J Catoggio, Marco Maradiaga-Ceceña, Patrick M Gaffney, Timothy J Vyse, Lindsey A Criswell, Betty P Tsao, Kathy L Sivils, Sang-Cheol Bae, Judith A James, Robert P Kimberly, Kenneth M Kaufman, John B Harley, Jorge A Esquivel-Valerio, José F Moctezuma, Mercedes A García, Guillermo A Berbotto, Alejandra M Babini, Hugo Scherbarth, Sergio Toloza, Vicente Baca, Swapan K Nath, Carlos Aguilar Salinas, Lorena Orozco, Teresa Tusié-Luna, Raphael Zidovetzki, Bernardo A Pons-Estel, Carl D Langefeld, Chaim O Jacob

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a strong genetic component. Our aim was to perform the first genome-wide association study on individuals from the Americas enriched for Native American heritage. We analyzed 3,710 individuals from four countries of Latin America and the Unites States diagnosed with SLE and healthy controls. Samples were genotyped with the HumanOmni1 BeadChip. Data of out-of-study controls was obtained for the HumanOmni2.5. Statistical analyses were performed using SNPTEST and SNPGWA. Data was adjusted for genomic control and FDR. Imputation was done using IMPUTE2, and HiBAG for classical HLA alleles. The IRF5-TNPO3 region showed the strongest association and largest odds ratio (OR) (rs10488631, Pgcadj = 2.61x10(-29) , OR = 2.12, 95% CI: 1.88-2.39) followed by the HLA class II on the DQA2-DQB1 loci (rs9275572, Pgcadj = 1.11 x 10(-16) , OR = 1.62, 95% CI: 1.46-1.80; rs9271366, Pgcadj =6.46 x 10(-12) , OR = 2.06, 95% CI: 1.71-2.50). Other known SLE loci associated were ITGAM, STAT4, TNIP1, NCF2 and IRAK1. We identified a novel locus on 10q24.33 (rs4917385, Pgcadj =1.4x10(-8) ) with a eQTL effect (Peqtl =8.0 x 10(-37) at USMG5/miR1307), and describe novel loci. We corroborate SLE-risk loci previously identified in European and Asians. Local ancestry estimation showed that HLA allele risk contribution is of European ancestral origin. Imputation of HLA alleles suggested that autochthonous Native American haplotypes provide protection. Our results show the insight gained by studying admixed populations to delineate the genetic architecture that underlies autoimmune and complex diseases. This article is protected by copyright. All rights reserved.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 106 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Mexico 1 <1%
Unknown 105 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 16 15%
Researcher 14 13%
Student > Bachelor 11 10%
Other 10 9%
Student > Master 9 8%
Other 20 19%
Unknown 26 25%
Readers by discipline Count As %
Medicine and Dentistry 23 22%
Biochemistry, Genetics and Molecular Biology 21 20%
Immunology and Microbiology 8 8%
Agricultural and Biological Sciences 6 6%
Engineering 3 3%
Other 13 12%
Unknown 32 30%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 November 2015.
All research outputs
#15,348,521
of 24,792,414 outputs
Outputs from Arthritis & Rheumatology
#2,038
of 2,989 outputs
Outputs of similar age
#161,404
of 307,096 outputs
Outputs of similar age from Arthritis & Rheumatology
#45
of 69 outputs
Altmetric has tracked 24,792,414 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,989 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 21.9. This one is in the 29th percentile – i.e., 29% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 307,096 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 46th percentile – i.e., 46% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 69 others from the same source and published within six weeks on either side of this one. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.