| Title: | Large-scale exome sequence analysis identifies sex- and age-specific determinants of obesity |
| Journal: | Cell Genomics |
| Published: | 2 Aug 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37601970/ |
| DOI: | https://doi.org/10.1016/j.xgen.2023.100362 |
| Citations: | 12 (12 in last 2 years) as of 8 Aug 2024 |
Publication 10207
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Obesity contributes substantially to the global burden of disease and has a significant heritable component. Recent large-scale exome sequencing studies identified several genes in which rare, protein-coding variants have large effects on adult body mass index (BMI). Here we extended such work by performing sex-stratified associations in the UK Biobank study (N∼420,000). We identified genes in which rare heterozygous loss-of-function increases adult BMI in women (DIDO1, PTPRG, and SLC12A5) and in men (SLTM), with effect sizes up to ∼8 kg/m2. This is complemented by analyses implicating rare variants in OBSCN and MADD for recalled childhood adiposity. The known functions of these genes, as well as findings of common variant genome-wide pathway enrichment analyses, suggest a role for neuron death, apoptosis, and DNA damage response mechanisms in the susceptibility to obesity across the life-course. These findings highlight the importance of considering sex-specific and life-course effects in the genetic regulation of obesity.</p>
18 Authors
- Lena R Kaisinger
- Katherine A Kentistou
- Stasa Stankovic
- Eugene J Gardner
- Felix R Day
- Yajie Zhao
- Alexander Mörseburg
- Christopher J Carnie
- Guido Zagnoli-Vieira
- Fabio Puddu
- Stephen P Jackson
- Stephen O'Rahilly
- I Sadaf Farooqi
- Laura Dearden
- Lucas C Pantaleão
- Susan E Ozanne
- Ken K Ong
- John R B Perry
1 Application
| Application ID | Title |
|---|---|
| 9905 | Using genetics to elucidate the relationship between socioeconomic/behavioural traits and disease |
Enabling scientific discoveries that improve human health