| Title: | The contribution of common and rare genetic variants to variation in metabolic traits in 288,137 East Asians |
| Journal: | Nature Communications |
| Published: | 4 Nov 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36333282/ |
| DOI: | https://doi.org/10.1038/s41467-022-34163-2 |
| URL: | https://www.nature.com/articles/s41467-022-34163-2.pdf |
Publication 10656
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Abstract
Metabolic traits are heritable phenotypes widely-used in assessing the risk of various diseases. We conduct a genome-wide association analysis (GWAS) of nine metabolic traits (including glycemic, lipid, liver enzyme levels) in 125,872 Korean subjects genotyped with the Korea Biobank Array. Following meta-analysis with GWAS from Biobank Japan identify 144 novel signals (MAF ≥ 1%), of which 57.0% are replicated in UK Biobank. Additionally, we discover 66 rare (MAF < 1%) variants, 94.4% of them co-incident to common loci, adding to allelic series. Although rare variants have limited contribution to overall trait variance, these lead, in carriers, substantial loss of predictive accuracy from polygenic predictions of disease risk from common variant alone. We capture groups with up to 16-fold variation in type 2 diabetes (T2D) prevalence by integration of genetic risk scores of fasting plasma glucose and T2D and the I349F rare protective variant. This study highlights the need to consider the joint contribution of both common and rare variants on inherited risk of metabolic traits and related diseases.</p>
15 Authors
- Young Jin Kim
- Sanghoon Moon
- Mi Yeong Hwang
- Sohee Han
- Hye-Mi Jang
- Jinhwa Kong
- Dong Mun Shin
- Kyungheon Yoon
- Sung Min Kim
- Jong-Eun Lee
- Anubha Mahajan
- Hyun-Young Park
- Mark I. McCarthy
- Yoon Shin Cho
- Bong-Jo Kim
1 Application
| Application ID | Title |
|---|---|
| 57705 | Identification and validation of diabetes, cardio-cerebrovascular disease, cancers related genetic factors based on Korea Biobank Array genome data |
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