Genome-wide association study of asthma in individuals of African ancestry reveals novel asthma susceptibility loci
Authors: Daya Michelle , Rafaels Nicholas , Chavan Sameer , Johnston Henry Richard , Shetty Aniket , Gignoux Christopher R. , Boorgula Meher Preethi , Campbell Monica , Maul Pissamai , Maul Trevor , Vergara Candelaria , Levin Albert M. , Wojcik Genevieve , Torgerson Dara G. , Ortega Victor E. , Doumatey Ayo , Araujo Maria Ilma , Avila Pedro C. , Bleecker Eugene , Bustamante Carlos , Caraballo Luis , Dunston Georgia M. , Faruque Mezbah U. , Ferguson Trevor S. , Figueiredo Camila , Ford Jean G. , Gourraud Pierre-Antoine , Hansel Nadia N. , Hernandez Ryan D. , Herrera-Paz Edwin Francisco , Kenny Eimear E. , Knight-Madden Jennifer , Kumar Rajesh , Lange Lesli A. , Lange Ethan M. , Lizee Antoine , Mayorga Alvaro , Meyers Deborah , Nicolae Dan L. , O’Connor Timothy D. , Oliveira Ricardo Riccio , Olopade Christopher O. , Olopade Olufunmilayo , Qin Zhaohui S. , Rotimi Charles , Watson Harold , Wilks Rainford J. , Williams L. Keoki , Wilson James G. , Ober Carole , Burchard Esteban G. , Beaty Terri H. , Taub Margaret A. , Ruczinski Ingo , Mathias Rasika Ann , Barnes Kathleen C. , Adegnika Ayola Akim , Arinola Ganiyu , Ateba-Ngoa Ulysse , Ayestas Gerardo , Correa Adolfo , De La Vega Francisco M. , Eng Celeste , Erazo Said Omar Leiva , Foreman Marilyn G. , Foster Cassandra , Gao Li , Gao Jingjing , Gietzen Kimberly , Grammer Leslie , Gutierrez Linda , Hansen Mark , Hartert Tina , Hu Yijuan , Kim Kwang-Youn A. , Landaverde-Torres Pamela , Marrugo Javier , Martinez Beatriz , Martinez Rosella , Mayorga Luis F. , Mejia-Mejia Delmy-Aracely , Meza Catherine , Musani Solomon , Musharoff Shaila , Oluwole Oluwafemi , Pino-Yanes Maria , Ramos Hector , Saenz Allan , Salzberg Steven , Samms-Vaughan Maureen , Schleimer Robert , Scott Alan F. , Shringarpure Suyash S. , Song Wei , Szpiech Zachary A. , Torres Raul , Varela Gloria , Vasquez Olga Marina , Ware Lorraine B. , Yazdanbakhsh Maria 
Published: March 2017

BACKGROUND

Asthma is a complex disease with striking disparities across racial and ethnic groups, which may be partly attributable to genetic factors. One of the main goals of the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to discover genes conferring risk to asthma in populations of African descent.

METHODS

We performed a genome-wide meta-analysis of asthma across 11 CAAPA datasets (4,827 asthma cases and 5,397 controls), genotyped on the African Diaspora Power Chip (ADPC) and including existing GWAS array data. The genotype data were imputed up to a whole genome sequence reference panel from n=880 African ancestry individuals for a total of 61,904,576 SNPs. Statistical models appropriate to each study design were used to test for association, and results were combined using the weighted Z-score method. We also used admixture mapping as a complementary approach to identify loci involved in asthma pathogenesis in subjects of African ancestry.

RESULTS

SNPs rs787160 and rs17834780 on chromosome 2q22.3 were significantly associated with asthma (p=6.57 × 10−9and 2.97 × 10−8, respectively). These SNPs lie in the intergenic region between the Rho GTPase Activating Protein 15 (ARHGAP15) and Glycosyltransferase Like Domain Containing 1 (GTDC1) genes. Four low frequency variants on chromosome 1q21.3, which may be involved in the “atopic march” and which are not polymorphic in Europeans, also showed evidence for association with asthma (1.18 ×10−6≤ p ≤ 3.06 ×10−6). SNP rs11264909 on chromosome 1q23.1, close to a region previously identified by the EVE asthma meta-analysis as having a putative African ancestry specific effect, only showed differences in counts in subjects homozygous for alleles of African ancestry. Admixture mapping also identified a significantly associated region on chromosome 6q23.2, which includes the Transcription Factor 21 (TCF21) gene, previously shown to be differentially expressed in bronchial tissues of asthmatics and non-asthmatics.

CONCLUSIONS

We have identified a number of novel asthma association signals warranting further investigation.