한빛사논문
- 조회322
Young Chan Lee1,2†, Sang‑Hyuk Jung1†, Manu Shivakumar1, Soojin Cha3, Woong‑Yang Park4, Hong‑Hee Won4,5, Young‑Gyu Eun2, Penn Medicine Biobank6 and Dokyoon Kim1,7*
1Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
2Department of Otolaryngology‑Head and Neck Surgery, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
3Hanyang University Institute for Rheumatology Research, Seoul, Republic of Korea.
4Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
5Samsung Medical Center, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
6Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
7Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, USA.
†Young Chan Lee and Sang-Hyuk Jung contributed equally as co-frst authors.
*Correspondence: Dokyoon Kim
Abstract
Background: Numerous observational studies have highlighted associations of genetic predisposition of head and neck squamous cell carcinoma (HNSCC) with diverse risk factors, but these findings are constrained by design limitations of observational studies. In this study, we utilized a phenome-wide association study (PheWAS) approach, incorporating a polygenic risk score (PRS) derived from a wide array of genomic variants, to systematically investigate phenotypes associated with genetic predisposition to HNSCC. Furthermore, we validated our findings across heterogeneous cohorts, enhancing the robustness and generalizability of our results.
Methods: We derived PRSs for HNSCC and its subgroups, oropharyngeal cancer and oral cancer, using large-scale genome-wide association study summary statistics from the Genetic Associations and Mechanisms in Oncology Network. We conducted a comprehensive investigation, leveraging genotyping data and electronic health records from 308,492 individuals in the UK Biobank and 38,401 individuals in the Penn Medicine Biobank (PMBB), and subsequently performed PheWAS to elucidate the associations between PRS and a wide spectrum of phenotypes.
Results: We revealed the HNSCC PRS showed significant association with phenotypes related to tobacco use disorder (OR, 1.06; 95% CI, 1.05-1.08; P = 3.50 × 10-15), alcoholism (OR, 1.06; 95% CI, 1.04-1.09; P = 6.14 × 10-9), alcohol-related disorders (OR, 1.08; 95% CI, 1.05-1.11; P = 1.09 × 10-8), emphysema (OR, 1.11; 95% CI, 1.06-1.16; P = 5.48 × 10-6), chronic airway obstruction (OR, 1.05; 95% CI, 1.03-1.07; P = 2.64 × 10-5), and cancer of bronchus (OR, 1.08; 95% CI, 1.04-1.13; P = 4.68 × 10-5). These findings were replicated in the PMBB cohort, and sensitivity analyses, including the exclusion of HNSCC cases and the major histocompatibility complex locus, confirmed the robustness of these associations. Additionally, we identified significant associations between HNSCC PRS and lifestyle factors related to smoking and alcohol consumption.
Conclusions: The study demonstrated the potential of PRS-based PheWAS in revealing associations between genetic risk factors for HNSCC and various phenotypic traits. The findings emphasized the importance of considering genetic susceptibility in understanding HNSCC and highlighted shared genetic bases between HNSCC and other health conditions and lifestyles.
논문정보
- Research article
- 2024년 03월 (BRIC 등록일 2024-03-18)
- 국내+국외 연구진
- 의약학 > 유전 및 유전체의학
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