| 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 |
Publication 10207
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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 |
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