title: Evaluation of European coeliac disease risk variants in a north Indian population.
abstract: Studies in European populations have contributed to a better understanding of the genetics of complex diseases, for example, in coeliac disease (CeD), studies of over 23 000 European samples have reported association to the HLA locus and another 39 loci. However, these associations have not been evaluated in detail in other ethnicities. We sought to better understand how disease-associated loci that have been mapped in Europeans translate to a disease risk for a population with a different ethnic background. We therefore performed a validation of European risk loci for CeD in 497 cases and 736 controls of north Indian origin. Using a dense-genotyping platform (Immunochip), we confirmed the strong association to the HLA region (rs2854275, P=8.2 × 10(-49)). Three loci showed suggestive association (rs4948256, P=9.3 × 10(-7), rs4758538, P=8.6 × 10(-5) and rs17080877, P=2.7 × 10(-5)). We directly replicated five previously reported European variants (P<0.05; mapping to loci harbouring FASLG/TNFSF18, SCHIP1/IL12A, PFKFB3/PRKCQ, ZMIZ1 and ICOSLG). Using a transferability test, we further confirmed association at PFKFB3/PRKCQ (rs2387397, P=2.8 × 10(-4)) and PTPRK/THEMIS (rs55743914, P=3.4 × 10(-4)). The north Indian population has a higher degree of consanguinity than Europeans and we therefore explored the role of recessively acting variants, which replicated the HLA locus (rs9271850, P=3.7 × 10(-23)) and suggested a role of additional four loci. To our knowledge, this is the first replication study of CeD variants in a non-European population.
authors: Department of Genetics, University of Delhi South Campus, New Delhi, India.
authors: Sabyasachi
authors: S
authors: Senapati
authors: Department of Genetics, University of Groningen, University Medical Hospital Groningen, Groningen, The Netherlands.
authors: Javier
authors: J
authors: Gutierrez-Achury
authors: Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India.
authors: Ajit
authors: A
authors: Sood
authors: Department of Medicine, Dayanand Medical College and Hospital, Ludhiana, India.
authors: Vandana
authors: V
authors: Midha
authors: Department of Genetics, University of Groningen, University Medical Hospital Groningen, Groningen, The Netherlands.
authors: Agata
authors: A
authors: Szperl
authors: Department of Genetics, University of Groningen, University Medical Hospital Groningen, Groningen, The Netherlands.
authors: Jihane
authors: J
authors: Romanos
authors: Department of Genetics, University of Groningen, University Medical Hospital Groningen, Groningen, The Netherlands.
authors: Alexandra
authors: A
authors: Zhernakova
authors: Department of Genetics, University of Groningen, University Medical Hospital Groningen, Groningen, The Netherlands.
authors: Lude
authors: L
authors: Franke
authors: Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country, Leioa, Spain.
authors: Santos
authors: S
authors: Alonso
authors: Department of Genetics, University of Delhi South Campus, New Delhi, India.
authors: B K
authors: BK
authors: Thelma
authors: Department of Genetics, University of Groningen, University Medical Hospital Groningen, Groningen, The Netherlands.
authors: Cisca
authors: C
authors: Wijmenga
authors: Department of Genetics, University of Groningen, University Medical Hospital Groningen, Groningen, The Netherlands.
authors: Gosia
authors: G
authors: Trynka
mesh_terms: D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics; D002446:Celiac Disease / Q000235:genetics*; D002874:Chromosome Mapping; D053222:Fas Ligand Protein / Q000235:genetics; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D007194:India; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000235:genetics; D053765:Interleukin-12 Subunit p35 / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics; D025481:Phosphofructokinase-2 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011493:Protein Kinase C / Q000235:genetics; D000074121:Protein Kinase C-theta; D015203:Reproducibility of Results; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics; D048069:Tumor Necrosis Factors / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C498514:ICOSLG protein, human; C508858:IL12A protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D053765:Interleukin-12 Subunit p35; D007527:Isoenzymes; C405019:SCHIP1 protein, human; C478967:TNFSF18 protein, human; D014157:Transcription Factors; D048069:Tumor Necrosis Factors; C480599:ZMIZ1 protein, human; C107345:PFKFB3 protein, human; D025481:Phosphofructokinase-2; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta