A Genome-Wide Association Study of a Hispanic Systemic Sclerosis Cohort

Lara Bossini-Castillo¹, Enrique Raya², John D. Reveille³, Shervin Assassi⁴, Olga Y Gorlova⁵, Dinesh Khanna⁶, Daniel E. Furst⁷, Suzanne Kafaja⁸, Robert W. Simms⁹, Robert Lafyatis⁹, Tracy M. Frech¹⁰, Virginia D. Steen¹¹, Barri J. Fessler¹², Jerry A. Molitor¹³, Marta Alarcón-Riquelme^14,15, Javier Martín¹⁶ and Maureen D Mayes⁴, ¹Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, PTS Granada, Granada, Spain, ²Rheumatology, Hospital Clínico San Cecilio, Granada, Spain, ³Internal Medicine/Rheumatology, University of Texas Medical School at Houston, Houston, TX, ⁴Rheumatology, University of Texas Medical School at Houston, Houston, TX, ⁵Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, ⁶Division of Rheumatology, University of Michigan, Ann Arbor, MI, ⁷Medicine, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, ⁸Rheumatology, University of California Los Angeles, Los Angeles, CA, ⁹Rheumatology, Boston University School of Medicine, Boston, MA, ¹⁰Div of Rheumatology, University of Utah, Salt Lake City, UT, ¹¹Department of Rheumatology, Georgetown University Medical Center, Washington, DC, ¹²Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, ¹³Rheumatology, University of Minnesota, Minneapolis, MN, ¹⁴Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma, OK, ¹⁵Centre for Genomics and Oncological Research (GENYO), Pfizer–University of Granada–Junta de Andalucia, Parque Tecnológico de la Salud (PTS), Granada, Spain, ¹⁶Instituto de Parasitología y Biomedicina López- Neyra, IPBLN-CSIC, PTS-Granada, Granada, Spain

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: GWAS, Hispanic patients, polymorphism and systemic sclerosis

Session Information

Date: Tuesday, November 10, 2015

Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's - Pathogenesis, Animal Models and Genetics Poster II

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Genome-wide association studies (GWASs) have resulted in the identification of several genetic loci involved in systemic sclerosis (SSc) susceptibility. However, GWASs are normally focused in white European ancestry populations. Indeed, in the case of SSc this hypothesis-free approach has not been followed in mixed populations such as Hispanic Americans. It should be considered that the genetic polymorphisms described in whites do not cover all the variation observed in other ethnic groups. Moreover, due to the difference linkage-disequilibrium patterns, the analysis of cohorts of multiple ancestries contributes to fine-mapping and causal variant identification. Therefore, the aim of our study was to analyze for the first time the genetic background of SSc in a Hispanic American population.

Methods: Our study comprised a total of 285 SSc patients and 261 ethnically matched healthy controls. All SSc cases and 131 controls were recruited in Houston (Texas, USA) and genotyped using the HumanOmni2.5-8 Illumina Array. Statistical power was increased by adding 130 additional controls of Hispanic descent, recruited in Oklahoma City (Oklahoma, USA) and genotyped using the HumanOmni1-Quad Illumina BeadChip. After stringent per variant and per individual quality controls, 307,939 single-nucleotide polymorphisms (SNPs) were included in our analysis. Despite the mixed ancestry of the Hispanic population in the USA, the majority of the analyzed individuals in our study, both cases and controls, were of Mexican origin. Nevertheless, stringent principal component analysis filters were applied to verify case-control overlap. Significance was calculated using 2×2 contingency tables and Fisher’s exact test or χ 2 when necessary, to obtain p-values, odds ratios and 95% confidence intervals using PLINK (v1.07) software. Genomic correction was used to correct for multiple testing.

Results: We observed genome-wide level associations in the HLA region, specifically in the HLA class II region (between the HLA-DRB1 and the HLA-DQA1 loci). However, we did not report any signal outside the HLA region that reached the genome-wide significance threshold. Nevertheless, we found nominally associated SNPs in a number of SSc-related loci, identified in white populations. The regions showing nominal associations included: IRF5, STAT4, CD247, BLK, BANK1, IRF8, IRF7, IL12A, ATG5, PPARG. It should be noted that, despite the replication of firm SSc-risk factors in the Hispanic population, the most associated variants for each loci were not normally the same than in white populations.

Conclusion: Our findings support a common genetic background for SSc susceptibility between white European and Hispanic populations. Nonetheless, our results also revealed that the associated variants were not necessarily the same in both populations. These findings may be a basis for causal variant identification in the shared loci.

Disclosure: L. Bossini-Castillo, None; E. Raya, None; J. D. Reveille, None; S. Assassi, None; O. Y. Gorlova, None; D. Khanna, None; D. E. Furst, Gilead, 2,GlaxoSmithKline, 2,NIH, 2,Novartis Pharmaceutical Corporation, 2,Pfizer Inc, 2,Roche Pharmaceuticals, 2,Genentech and Biogen IDEC Inc., 2,UCB, 2,Abbvie, 5,Actelion Pharmaceuticals US, 5,Amgen, 5,Bristol-Myers Squibb, 5,Cytori, 5,Janssen Pharmaceutica Product, L.P., 5,Gilead, 5,GlaxoSmithKline, 5,NIH, 5,Novartis Pharmaceutical Corporation, 5,Pfizer Inc, 5,Roche Pharmaceuticals, 5,Genentech and Biogen IDEC Inc., 5,UCB, 5,Abbvie, 8,Actelion Pharmaceuticals US, 8,Bristol-Myers Squibb, 2,Amgen, 2,Actelion Pharmaceuticals US, 2,Abbvie, 2,UCB, 8; S. Kafaja, None; R. W. Simms, None; R. Lafyatis, None; T. M. Frech, None; V. D. Steen, None; B. J. Fessler, None; J. A. Molitor, None; M. Alarcón-Riquelme, None; J. Martín, None; M. D. Mayes, None.

To cite this abstract in AMA style:

Bossini-Castillo L, Raya E, Reveille JD, Assassi S, Gorlova OY, Khanna D, Furst DE, Kafaja S, Simms RW, Lafyatis R, Frech TM, Steen VD, Fessler BJ, Molitor JA, Alarcón-Riquelme M, Martín J, Mayes MD. A Genome-Wide Association Study of a Hispanic Systemic Sclerosis Cohort [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/a-genome-wide-association-study-of-a-hispanic-systemic-sclerosis-cohort/. Accessed .

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