Details

Autor(en) / Beteiligte

• Akbari, Parsa
• Sosina, Olukayode A
• Bovijn, Jonas
• Landheer, Karl
• Nielsen, Jonas B
• Kim, Minhee
• Aykul, Senem
• De, Tanima
• Haas, Mary E
• Hindy, George
• Lin, Nan
• Dinsmore, Ian R
• Luo, Jonathan Z
• Hectors, Stefanie
• Geraghty, Benjamin
• Germino, Mary
• Panagis, Lampros
• Parasoglou, Prodromos
• Walls, Johnathon R
• Halasz, Gabor
• Atwal, Gurinder S
• Jones, Marcus
• LeBlanc, Michelle G
• Still, Christopher D
• Carey, David J
• Giontella, Alice
• Orho-Melander, Marju
• Berumen, Jaime
• Kuri-Morales, Pablo
• Alegre-Díaz, Jesus
• Torres, Jason M
• Emberson, Jonathan R
• Collins, Rory
• Rader, Daniel J
• Zambrowicz, Brian
• Murphy, Andrew J
• Balasubramanian, Suganthi
• Overton, John D
• Reid, Jeffrey G
• Shuldiner, Alan R
• Cantor, Michael
• Abecasis, Goncalo R
• Ferreira, Manuel A R
• Sleeman, Mark W
• Gusarova, Viktoria
• Altarejos, Judith
• Harris, Charles
• Economides, Aris N
• Idone, Vincent
• Karalis, Katia
• Della Gatta, Giusy
• Mirshahi, Tooraj
• Yancopoulos, George D
• Melander, Olle
• Marchini, Jonathan
• Tapia-Conyer, Roberto
• Locke, Adam E
• Baras, Aris
• Verweij, Niek
• Lotta, Luca A

Titel

Multiancestry exome sequencing reveals INHBE mutations associated with favorable fat distribution and protection from diabetes

Ist Teil von

• Nature communications, 2022-08, Vol.13 (1), p.4844-4844, Article 4844

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• Body fat distribution is a major, heritable risk factor for cardiometabolic disease, independent of overall adiposity. Using exome-sequencing in 618,375 individuals (including 160,058 non-Europeans) from the UK, Sweden and Mexico, we identify 16 genes associated with fat distribution at exome-wide significance. We show 6-fold larger effect for fat-distribution associated rare coding variants compared with fine-mapped common alleles, enrichment for genes expressed in adipose tissue and causal genes for partial lipodystrophies, and evidence of sex-dimorphism. We describe an association with favorable fat distribution (p = 1.8 × 10 ), favorable metabolic profile and protection from type 2 diabetes (~28% lower odds; p = 0.004) for heterozygous protein-truncating mutations in INHBE, which encodes a circulating growth factor of the activin family, highly and specifically expressed in hepatocytes. Our results suggest that inhibin βE is a liver-expressed negative regulator of adipose storage whose blockade may be beneficial in fat distribution-associated metabolic disease.