Influence of Diabetes Family History on the Associations of Combined Genetic and Lifestyle Risks with Diabetes in the Tohoku Medical Megabank Community-Based Cohort Study

• Published in: Journal of Atherosclerosis and Thrombosis 2023/12/01, Vol.30(12), pp.1950-1965
• Main Authors: Takase, Masato, Nakaya, Naoki, Nakamura, Tomohiro, Kogure, Mana, Hatanaka, Rieko, Nakaya, Kumi, Chiba, Ippei, Kanno, Ikumi, Nochioka, Kotaro, Tsuchiya, Naho, Hirata, Takumi, Narita, Akira, Obara, Taku, Ishikuro, Mami, Uruno, Akira, Kobayashi, Tomoko, Kodama, Eiichi N, Hamanaka, Yohei, Orui, Masatsugu, Ogishima, Soichi, Nagaie, Satoshi, Fuse, Nobuo, Sugawara, Junichi, Kuriyama, Shinichi, Tsuji, Ichiro, Tamiya, Gen, Hozawa, Atsushi, Yamamoto, Masayuki
• Format: Article
• Language: English
• Subjects: Cohort Studies; Cross-Sectional Studies; Diabetes mellitus; Diabetes Mellitus - epidemiology; Diabetes Mellitus - genetics; Epidemiology; Family history; Genetic; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Life Style; Lifestyle; Risk Factors
• ISSN: 1340-3478; 1880-3873
• DOI: 10.5551/jat.64425

Aim: The influence of family history of diabetes, probably reflecting genetic and lifestyle factors, on the association of combined genetic and lifestyle risks with diabetes is unknown. We examined these associations.Methods: This cross-sectional study included 9,681 participants in the Tohoku Medical Megabank Community-based Cohort Study. A lifestyle score, which was categorized into ideal, intermediate, and poor lifestyles, was given. Family history was obtained through a self-reported questionnaire. A polygenic risk score (PRS) was constructed in the target data (n=1,936) using publicly available genome-wide association study summary statistics from BioBank Japan. For test data (n=7,745), we evaluated PRS performance and examined the associations of combined family history and genetic and lifestyle risks with diabetes. Diabetes was defined as non-fasting blood glucose ≥ 200 mmHg, HbA1c ≥ 6.5%, and/or self-reported diabetes treatment.Results: In test data, 467 (6.0%) participants had diabetes. Compared with a low genetic risk and an ideal lifestyle without a family history, the odds ratio (OR) was 3.73 (95% confidence interval [CI], 1.92–7.00) for a lower genetic risk and a poor lifestyle without a family history. Family history was significantly associated with diabetes (OR, 3.58 [95% CI, 1.73–6.98]), even in those with a low genetic risk and an ideal lifestyle. Even among participants who had an ideal lifestyle without a family history, a high genetic risk was associated with diabetes (OR, 2.49 [95% CI, 1.65–3.85]). Adding PRS to family history and conventional lifestyle risk factors improved the prediction ability for diabetes.Conclusions: Our findings support the notion that a healthy lifestyle is important to prevent diabetes regardless of genetic risk.