Journal Article

DKFZ-2021-01535

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Search for AL amyloidosis risk factors using Mendelian randomization.

Saunders, C. N. ; Chattopadhyay, S. ; Huhn, S. ; Weinhold, N. ; Hoffmann, P. ; Nöthen, M. M. ; Jöckel, K.-H. ; Schmidt, B. ; Landi, S. ; Goldschmidt, H. ; Milani, P. ; Merlini, G. ; Rowcieno, D. ; Hawkins, P. ; Hegenbart, U. ; Palladini, G. ; Wechalekar, A. ; Schönland, S. O. ; Försti, A.DKFZ* ; Houlston, R. ; Hemminki, K.DKFZ*

2021
American Society of Hematology Washington, DC

This record in other databases:  

Please use a persistent id in citations: doi:10.1182/bloodadvances.2021004423

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.

Note: 2021 Jul 13;5(13):2725-2731

---

Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2021

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF < 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---