Details

Autor(en) / Beteiligte

• Turcot, Valérie
• Lu, Yingchang
• Highland, Heather M
• Schurmann, Claudia
• Justice, Anne E
• Fine, Rebecca S
• Bradfield, Jonathan P
• Esko, Tõnu
• Giri, Ayush
• Graff, Mariaelisa
• Guo, Xiuqing
• Hendricks, Audrey E
• Karaderi, Tugce
• Lempradl, Adelheid
• Locke, Adam E
• Mahajan, Anubha
• Marouli, Eirini
• Sivapalaratnam, Suthesh
• Young, Kristin L
• Alfred, Tamuno
• Feitosa, Mary F
• Masca, Nicholas GD
• Manning, Alisa K
• Medina-Gomez, Carolina
• Mudgal, Poorva
• Ng, Maggie CY
• Reiner, Alex P
• Vedantam, Sailaja
• Willems, Sara M
• Winkler, Thomas W
• Abecasis, Goncalo
• Aben, Katja K
• Alam, Dewan S
• Alharthi, Sameer E
• Allison, Matthew
• Amouyel, Philippe
• Asselbergs, Folkert W
• Auer, Paul L
• Balkau, Beverley
• Bang, Lia E
• Barroso, Inês
• Bastarache, Lisa
• Benn, Marianne
• Bergmann, Sven
• Bielak, Lawrence F
• Blüher, Matthias
• Boehnke, Michael
• Boeing, Heiner
• Boerwinkle, Eric
• Böger, Carsten A
• Bork-Jensen, Jette
• Bots, Michiel L
• Bottinger, Erwin P
• Bowden, Donald W
• Brandslund, Ivan
• Breen, Gerome
• Brilliant, Murray H
• Broer, Linda
• Brumat, Marco
• Burt, Amber A
• Butterworth, Adam S
• Campbell, Peter T
• Cappellani, Stefania
• Carey, David J
• Catamo, Eulalia
• Caulfield, Mark J
• Chambers, John C
• Chasman, Daniel I
• Chen, Yii-Der Ida
• Chowdhury, Rajiv
• Christensen, Cramer
• Chu, Audrey Y
• Cocca, Massimiliano
• Collins, Francis S
• Cook, James P
• Corley, Janie
• Galbany, Jordi Corominas
• Cox, Amanda J
• Crosslin, David S
• Cuellar-Partida, Gabriel
• D'Eustacchio, Angela
• Danesh, John
• Davies, Gail
• de Bakker, Paul IW
• de Groot, Mark CH
• de Mutsert, Renée
• Deary, Ian J
• Dedoussis, George
• Demerath, Ellen W
• den Heijer, Martin
• den Hollander, Anneke I
• den Ruijter, Hester M
• Dennis, Joe G
• Denny, Josh C
• Di Angelantonio, Emanuele
• Drenos, Fotios
• Du, Mengmeng
• Dubé, Marie-Pierre
• Dunning, Alison M
• Easton, Douglas F

Titel

Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure underpinning obesity

Ist Teil von

• Nature genetics, 2017-12, Vol.50 (1), p.26-41

Erscheinungsjahr

2017

Beschreibungen/Notizen

• Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, non-coding variants from which pinpointing causal genes remains challenging. Here, we combined data from 718,734 individuals to discover rare and low-frequency (MAF<5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which eight in genes ( ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2, ZNF169 ) newly implicated in human obesity, two ( MC4R, KSR2 ) previously observed in extreme obesity, and two variants in GIPR . Effect sizes of rare variants are ~10 times larger than of common variants, with the largest effect observed in carriers of an MC4R stop-codon (p.Tyr35Ter, MAF=0.01%), weighing ~7kg more than non-carriers. Pathway analyses confirmed enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically-supported therapeutic targets to treat obesity.