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@ARTICLE{Saunders:169730,
author = {C. N. Saunders and S. Chattopadhyay and S. Huhn and N.
Weinhold and P. Hoffmann and M. M. Nöthen and K.-H. Jöckel
and B. Schmidt and S. Landi and H. Goldschmidt and P. Milani
and G. Merlini and D. Rowcieno and P. Hawkins and U.
Hegenbart and G. Palladini and A. Wechalekar and S. O.
Schönland and A. Försti$^*$ and R. Houlston and K.
Hemminki$^*$},
title = {{S}earch for {AL} amyloidosis risk factors using
{M}endelian randomization.},
journal = {Blood advances},
volume = {5},
number = {13},
issn = {2473-9537},
address = {Washington, DC},
publisher = {American Society of Hematology},
reportid = {DKFZ-2021-01535},
pages = {2725 - 2731},
year = {2021},
note = {2021 Jul 13;5(13):2725-2731},
abstract = {In amyloid light chain (AL) amyloidosis, amyloid fibrils
derived from immunoglobulin light chain are deposited in
many organs, interfering with their function. The etiology
of AL amyloidosis is poorly understood. Summary data from
genome-wide association studies (GWASs) of multiple
phenotypes can be exploited by Mendelian randomization (MR)
methodology to search for factors influencing AL amyloidosis
risk. We performed a 2-sample MR analyzing 72 phenotypes,
proxied by 3461 genetic variants, and summary genetic data
from a GWAS of 1129 AL amyloidosis cases and 7589 controls.
Associations with a Bonferroni-defined significance level
were observed for genetically predicted increased monocyte
counts (P = 3.8 × 10-4) and the tumor necrosis factor
receptor superfamily member 17 (TNFRSF17) gene (P = 3.4 ×
10-5). Two other associations with the TNFRSF (members 6 and
19L) reached a nominal significance level. The association
between genetically predicted decreased fibrinogen levels
may be related to roles of fibrinogen other than blood
clotting. be related to its nonhemostatic role. It is
plausible that a causal relationship with monocyte
concentration could be explained by selection of a light
chain-producing clone during progression of monoclonal
gammopathy of unknown significance toward AL amyloidosis.
Because TNFRSF proteins have key functions in lymphocyte
biology, it is entirely plausible that they offer a
potential link to AL amyloidosis pathophysiology. Our study
provides insight into AL amyloidosis etiology, suggesting
high circulating levels of monocytes and TNFRSF proteins as
risk factors.},
cin = {B062 / HD01},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34228109},
doi = {10.1182/bloodadvances.2021004423},
url = {https://inrepo02.dkfz.de/record/169730},
}