**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Mette Christoffersen, MSc PhD
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital
Copenhagen, Denmark

**Main Body of the Abstract**
Background:
In plasma, transthyretin circulates as a tetramer with the main function to transport retinol-binding protein and thyroxine. Older age, female sex and inflammation are associated with lower concentrations of plasma transthyretin, while high alcohol consumption and elevated triglyceride levels are associated with higher concentrations. Aside from structural genetic variants in the TTR gene which affect transthyretin tetramer stability and thereby have a secondary effect on plasma transthyretin concentration, genetic determinants of plasma transthyretin concentration are unknown. We aimed to conduct a genome-wide association study (GWAS) to reveal novel genetic determinants of plasma transthyretin concentration.
Methods:
We genotyped and measured plasma transthyretin concentrations in 17,000 individuals from two studies of the Danish general population, the Copenhagen City Heart Study (CCHS) and the Copenhagen General Population Study (CGPS). We first performed GWAS’ on plasma transthyretin concentrations in the CCHS and CGPS separately. Second, we meta-analyzed results from the two studies.
Results:
The GWAS’ from the CCHS and CGPS both confirmed the TTR locus as a genetic determinant of plasma transthyretin concentrations (P=3x10-24). The meta-analysis of the two studies further revealed two novel loci mapped to the CYP4V2 and MAF genes (P=4x10-9 and P=3x10-12) (Figure). CYP4V2 is known to be involved in fatty acid metabolism, while MAF has been associated to thyroid-stimulating hormone, thyroid volume, hyperthyroidism, and thyroid function.
Conclusions:
We conducted the first GWAS’ of plasma transthyretin concentration. The studies confirmed the TTR locus, and a meta-analysis further revealed two novel loci previously associated with lipid metabolism and thyroid function.



**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Mette Christoffersen, MSc PhD
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital
Copenhagen, Denmark

**Main Body of the Abstract**
**Background:**
In plasma, transthyretin circulates as a tetramer with the main function to transport retinol-binding protein and thyroxine. Older age, female sex and inflammation are associated with lower concentrations of plasma transthyretin, while high alcohol consumption and elevated triglyceride levels are associated with higher concentrations. Aside from structural genetic variants in the _TTR_ gene which affect transthyretin tetramer stability and thereby have a secondary effect on plasma transthyretin concentration, genetic determinants of plasma transthyretin concentration are unknown. We aimed to conduct a genome-wide association study (GWAS) to reveal novel genetic determinants of plasma transthyretin concentration.
**Methods:**
We genotyped and measured plasma transthyretin concentrations in 17,000 individuals from two studies of the Danish general population, the Copenhagen City Heart Study (CCHS) and the Copenhagen General Population Study (CGPS). We first performed GWAS’ on plasma transthyretin concentrations in the CCHS and CGPS separately. Second, we meta-analyzed results from the two studies.
**Results:**
The GWAS’ from the CCHS and CGPS both confirmed the _TTR_ locus as a genetic determinant of plasma transthyretin concentrations (P=3x10^-24^). The meta-analysis of the two studies further revealed two novel loci mapped to the _CYP4V2_ and _MAF_ genes (P=4x10^-9^ and P=3x10^-12^) (**Figure**). _CYP4V2_ is known to be involved in fatty acid metabolism, while _MAF_ has been associated to thyroid-stimulating hormone, thyroid volume, hyperthyroidism, and thyroid function.
**Conclusions:**
We conducted the first GWAS’ of plasma transthyretin concentration. The studies confirmed the _TTR_ locus, and a meta-analysis further revealed two novel loci previously associated with lipid metabolism and thyroid function.



First genome-wide association study of plasma transthyretin concentration PB68 (#203)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.