Exploring genetic regulation of immunoglobulin A northwesternu NatureComms
. Interestingly, we detected no significant causal effects between serum IgA levels and Celiac disease or BMI. In reverse causality analyses we observed no causal effect of Celiac disease on serum IgA levels, however, there was a highly significant causal effect of BMI on serum IgA levels . In sensitivity analyses, there was evidence of directional pleiotropy , but the causal effect of BMI became stronger and more significant when the balanced pleiotropy assumption was relaxed .
Previous smaller GWAS for serum IgA levels have been limited to European or East Asian ancestry, while African and other ancestries have not been included in these studies. Our multi-ethnic cohort included four diverse ancestral groups and allowed us to demonstrate that African ancestry was associated with higher serum IgA levels compared to other ancestries.
In the analysis of genetic relationships with other traits, we observed shared polygenic determination between IgA levels and several immune, infections, renal, and cardio-metabolic traits. Our findings support the protective role of IgA in susceptibility to various infectious pathogens as well as inflammatory bowel disease. At the same time, we observed a positive genetic correlation between IgA levels and IgA nephropathy, a common form of kidney disease due to IgA deposition.
In summary, we reported 20 genome-wide significant loci associated with serum IgA levels, and we prioritized potential effector genes and cell types for 70% of the loci. We demonstrated that IgA levels are positively correlated with African ancestry.
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