Predicted loss of function alleles in Bassoon (BSN) are associated with obesity
Bassoon ( BSN ) is a component of a hetero-dimeric presynaptic cytomatrix protein that orchestrates neurotransmitter release with Piccolo ( PCLO ) from glutamatergic neurons throughout the brain. Heterozygous missense variants in BSN have previously been associated with neurodegenerative disorders in humans. We performed an exome-wide association analysis of ultra-rare variants in about 140,000 unrelated individuals from the UK Biobank to search for new genes associated with obesity. We found that rare heterozygous predicted loss of function (pLoF) variants in BSN are associated with higher BMI with log10-p value of 11.78 in the UK biobank cohort. The association was replicated in the All of Us whole genome sequencing data. Additionally, we have identified two individuals (one of whom has a de novo variant) with a heterozygous pLoF variant in a cohort of early onset or extreme obesity at Columbia University. Like the individuals identified in the UKBB and All of us Cohorts, these individuals have no history of neurobehavioral or cognitive disability. Heterozygosity for pLoF BSN variants constitutes a new etiology for obesity.
| Errataetall: |
UpdateIn: NPJ Genom Med. 2023 Oct 21;8(1):33. - PMID 37865656 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
|---|---|
| Enthalten in: |
medRxiv : the preprint server for health sciences - (2023) vom: 23. Feb. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zhu, Na [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Revised 04.12.2023 published: Electronic UpdateIn: NPJ Genom Med. 2023 Oct 21;8(1):33. - PMID 37865656 Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.1101/2023.02.19.23285978 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM353711721 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM353711721 | ||
| 003 | DE-627 | ||
| 005 | 20231226060633.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2023.02.19.23285978 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1178.xml |
| 035 | |a (DE-627)NLM353711721 | ||
| 035 | |a (NLM)36865254 | ||
| 035 | |a (PII)2023.02.19.23285978 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Zhu, Na |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Predicted loss of function alleles in Bassoon (BSN) are associated with obesity |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 04.12.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a UpdateIn: NPJ Genom Med. 2023 Oct 21;8(1):33. - PMID 37865656 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Bassoon ( BSN ) is a component of a hetero-dimeric presynaptic cytomatrix protein that orchestrates neurotransmitter release with Piccolo ( PCLO ) from glutamatergic neurons throughout the brain. Heterozygous missense variants in BSN have previously been associated with neurodegenerative disorders in humans. We performed an exome-wide association analysis of ultra-rare variants in about 140,000 unrelated individuals from the UK Biobank to search for new genes associated with obesity. We found that rare heterozygous predicted loss of function (pLoF) variants in BSN are associated with higher BMI with log10-p value of 11.78 in the UK biobank cohort. The association was replicated in the All of Us whole genome sequencing data. Additionally, we have identified two individuals (one of whom has a de novo variant) with a heterozygous pLoF variant in a cohort of early onset or extreme obesity at Columbia University. Like the individuals identified in the UKBB and All of us Cohorts, these individuals have no history of neurobehavioral or cognitive disability. Heterozygosity for pLoF BSN variants constitutes a new etiology for obesity | ||
| 650 | 4 | |a Preprint | |
| 700 | 1 | |a LeDuc, Charles A |e verfasserin |4 aut | |
| 700 | 1 | |a Fennoy, Ilene |e verfasserin |4 aut | |
| 700 | 1 | |a Laferr Re, Blandine |e verfasserin |4 aut | |
| 700 | 1 | |a Doege, Claudia A |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Yufeng |e verfasserin |4 aut | |
| 700 | 1 | |a Chung, Wendy K |e verfasserin |4 aut | |
| 700 | 1 | |a Leibel, Rudolph L |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t medRxiv : the preprint server for health sciences |d 2020 |g (2023) vom: 23. Feb. |w (DE-627)NLM310900166 |7 nnns |
| 773 | 1 | 8 | |g year:2023 |g day:23 |g month:02 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2023.02.19.23285978 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2023 |b 23 |c 02 | ||