Abstract
Non-inherited maternal antigens encoded by specific HLA-DRB1 alleles (NIMA) have been implicated as a rheumatoid arthritis (RA) risk factor. Using genotype data from North American Rheumatoid Arthritis Consortium study participants and the maternal-fetal genotype incompatibility (MFG) test, we find evidence for offspring allelic effects but no evidence for NIMA as a RA risk factor. We discuss possible reasons why our result conflicts with several previous studies (including one of our own) that used RA patients from northern Europe.
Highlights
Rheumatoid arthritis (RA) is highly associated with HLADRB1 *0101, *0102, *0401, *0404, *0405, *0408, *0423, *10, *1001, *1402, and *1406 alleles that encode a shared epitope (SE) [1]
Hsieh et al [3] demonstrated that the maternal-fetal genotype incompatibility (MFG) test [9,10] allows the joint estimation of the offspring allelic and NIMA effects as a rheumatoid arthritis (RA) risk factor and is robust to population stratification
Inference We fit three models by placing different constraints on the parameters. These models are compared by constructing likelihood-ratio test statistics
Summary
Rheumatoid arthritis (RA) is highly associated with HLADRB1 *0101, *0102, *0401, *0404, *0405, *0408, *0423, *10, *1001, *1402, and *1406 alleles that encode a shared epitope (SE) [1]. As many as 30% of the patients do not carry SE coding alleles [1] and an association between non-inherited maternal SE HLA-DRB1 antigen coding alleles (NIMA) and RA has been observed [2,3,4,5] One explanation for the latter finding is that NIMA may be involved in RA pathogenesis through microchimera formation in offspring who do not have SE coding alleles [2]. Hsieh et al [3] demonstrated that the maternal-fetal genotype incompatibility (MFG) test [9,10] allows the joint estimation of the offspring allelic and NIMA effects as a RA risk factor and is robust to population stratification. The current study applies the MFG test to HLA-DRB1 genotype data from the North American Rheumatoid Arthri-
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