Rare predicted loss of function alleles in Bassoon (BSN) are associated with obesity

Ward, Z. J. et al. Projected U.S. state-level prevalence of adult obesity and severe obesity. N. Engl. J. Med 381, 2440–2450 (2019).

Article  PubMed  Google Scholar 

National Health and Nutrition Examination Survey 2017–March 2020 Prepandemic Data Files Development of Files and Prevalence Estimates for Selected Health Outcomes. in National Health Statistics Reports (ed. National Center for Health, S.) (https://doi.org/10.15620/cdc:106273, Hyattsville, MD, 2021).

Llewellyn, C. H., Trzaskowski, M., Plomin, R. & Wardle, J. Finding the missing heritability in pediatric obesity: the contribution of genome-wide complex trait analysis. Int. J. Obes. 37, 1506–1509 (2013).

Article  CAS  Google Scholar 

Loos, R. J. F. & Janssens, A. C. J. W. Predicting polygenic obesity using genetic information. Cell Metab. 25, 535–543 (2017).

Article  CAS  PubMed  Google Scholar 

Luke, A. et al. Heritability of obesity-related traits among Nigerians, Jamaicans and US black people. Int. J. Obes. 25, 1034–1041 (2001).

Article  CAS  Google Scholar 

Maes, H. H. M., Neale, M. C. & Eaves, L. J. Genetic and environmental factors in relative body weight and human adiposity. Behav. Genet. 27, 325–351 (1997).

Article  CAS  PubMed  Google Scholar 

Albuquerque, D., Nobrega, C., Manco, L. & Padez, C. The contribution of genetics and environment to obesity. Br. Med. Bull. 123, 159–173 (2017).

Article  PubMed  Google Scholar 

Wang, K. et al. A genome-wide association study on obesity and obesity-related traits. PLoS One 6, e18939 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Speakman, J. R., Loos, R. J. F., O’Rahilly, S., Hirschhorn, J. N. & Allison, D. B. GWAS for BMI: a treasure trove of fundamental insights into the genetic basis of obesity. Int J. Obes. (Lond.) 42, 1524–1531 (2018).

Article  CAS  PubMed  Google Scholar 

Scuteri, A. et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 3, e115 (2007).

Article  PubMed  PubMed Central  Google Scholar 

Khera, A. V. et al. Polygenic prediction of weight and obesity trajectories from birth to adulthood. Cell 177, 587–596.e9 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Loos, R. J. F. & Yeo, G. S. H. The genetics of obesity: from discovery to biology. Nat. Rev. Genet 23, 120–133 (2022).

Article  CAS  PubMed  Google Scholar 

Loos, R. J. The genetics of adiposity. Curr. Opin. Genet Dev. 50, 86–95 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Marouli, E. et al. Rare and low-frequency coding variants alter human adult height. Nature 542, 186–190 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lanktree, M. B. et al. Meta-analysis of dense genecentric association studies reveals common and uncommon variants associated with height. Am. J. Hum. Genet. 88, 6–18 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Trynka, G. et al. Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nat. Genet. 43, 1193–U45 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stitziel, N. O. et al. Exome sequencing in suspected monogenic dyslipidemias. Circ-Cardiovasc Genet. 8, 343–50 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Goodrich, J. K. et al. Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes. Nat. Commun. 12, 3505 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wilding, J. P. H., Calanna, S. & Kushner, R. F. Once-weekly semaglutide in adults with overweight or obesity. Reply. N. Engl. J. Med 385, e4 (2021).

Article  PubMed  Google Scholar 

Musunuru, K. et al. Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia. N. Engl. J. Med 363, 2220–7 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bycroft, C. et al. The UK Biobank resource with deep phenotyping and genomic data. Nature 562, 203–209 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Backman, J. D. et al. Exome sequencing and analysis of 454,787 UK Biobank participants. Nature 599, 628–634 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gill, R. et al. Whole-exome sequencing identifies novel LEPR mutations in individuals with severe early onset obesity. Obesity 22, 576–584 (2014).

Article  CAS  PubMed  Google Scholar 

Mbatchou, J. et al. Computationally efficient whole-genome regression for quantitative and binary traits. Nat. Genet 53, 1097–1103 (2021).

Article  CAS  PubMed  Google Scholar 

De Rosa, M. C. et al. Gene expression atlas of energy balance brain regions. Jci Insight 6, e149137 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Zhai, R. et al. Temporal appearance of the presynaptic cytomatrix protein bassoon during synaptogenesis. Mol. Cell. Neurosci. 15, 417–428 (2000).

Article  CAS  PubMed  Google Scholar 

Schoch, S. & Gundelfinger, E. D. Molecular organization of the presynaptic active zone. Cell Tissue Res. 326, 379–391 (2006).

Article  CAS  PubMed  Google Scholar 

Altrock, W. D. et al. Functional inactivation of a fraction of excitatory synapses in mice deficient for the active zone protein bassoon. Neuron 37, 787–800 (2003).

Article  CAS  PubMed  Google Scholar 

Angenstein, F. et al. Manganese-enhanced MRI reveals structural and functional changes in the cortex of bassoon mutant mice. Cereb. Cortex 17, 28–36 (2007).

Article  PubMed  Google Scholar 

Gundelfinger, E. D., Reissner, C. & Garner, C. C. Role of bassoon and piccolo in assembly and molecular organization of the active zone. Front Synaptic Neurosci. 7, 19 (2015).

PubMed  Google Scholar 

Hallermann, S. et al. Bassoon speeds vesicle reloading at a central excitatory synapse. Neuron 68, 710–723 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Waites, C. L. et al. Bassoon and Piccolo maintain synapse integrity by regulating protein ubiquitination and degradation. Embo J. 32, 954–969 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hashida, H. et al. Cloning and mapping of ZNF231, a novel brain-specific gene encoding neuronal double zinc finger protein whose expression is enhanced in a neurodegenerative disorder, multiple system atrophy (MSA). Genomics 54, 50–58 (1998).

Article  CAS  PubMed  Google Scholar 

Montenegro-Venegas, C., Annamneedi, A., Hoffmann-Conaway, S., Gundelfinger, E. D. & Garner, C. C. BSN (bassoon) and PRKN/parkin in concert control presynaptic vesicle autophagy. Autophagy 16, 1732–1733 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yabe, I. et al. Mutations in bassoon in individuals with familial and sporadic progressive supranuclear palsy-like syndrome. Sci. Rep. 8, 819 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Zheng, H. & Berthoud, H. R. Neural systems controlling the drive to eat: mind versus metabolism. Physiol. (Bethesda) 23, 75–83 (2008).

CAS  Google Scholar 

Shah, B. P. et al. MC4R-expressing glutamatergic neurons in the paraventricular hypothalamus regulate feeding and are synaptically connected to the parabrachial nucleus. Proc. Natl Acad. Sci. USA 111, 13193–13198 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fenselau, H. et al. A rapidly acting glutamatergic ARC -> PVH satiety circuit postsynaptically regulated by alpha-MSH. Nat. Neurosci. 20, 42–51 (2017).

Article  CAS  PubMed  Google Scholar 

Claflin, K. E. et al. Pharmacological FGF21 signals to glutamatergic neurons to enhance

Comments (0)

No login
gif