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OBJECTIVE: The Programmed Cell Death 1 gene (PDCD1) on chromosome 2q37.3 encodes PD-1 which is involved in providing a negative signal to activated T cells. Large case-control studies have shown association of PDCD1 with several autoimmune diseases although, to date, no such studies have been performed for Graves' disease (GD). The objective of our study was to investigate eight tag SNPs representing the majority of common variation in PDCD1 within a well-characterized large UK Caucasian GD dataset. DESIGN: A case control association study of eight polymorphisms. PATIENTS: 2671 Graves' disease patients and 864 controls. MEASUREMENTS: Tests for association with disease. RESULTS: No association with disease was seen for any of the +4163, +5049, +5318, +5640, +5678 and +7078 SNPs genotyped in this study. Association was detected between the +2375 SNP (P = 0.021, OR = 1.14 [95% CI = 1.01-1.29]) and GD and a small protective effect was seen with the +6799 SNP genotypes (P = 0.028, OR = 0.77 [95% CI = 0.58-1.03]). CONCLUSIONS: This study has, for the first time, shown that small effects within PDCD1 may contribute towards the development of GD, supporting the hypothesis that much of the currently unknown genetic contribution to GD could be due to several small genetic effects with ORs 1.2. Replication of this result is now needed to confirm our findings and justify more detailed fine mapping of a primary aetiological variant in this gene region.

Original publication




Journal article


Clin Endocrinol (Oxf)

Publication Date





125 - 128


Antigens, CD, Apoptosis Regulatory Proteins, Case-Control Studies, Chi-Square Distribution, Databases, Genetic, Gene Frequency, Genotype, Graves Disease, Humans, Odds Ratio, Polymorphism, Single Nucleotide, Programmed Cell Death 1 Receptor, Risk