Genetic Risk, Lifestyle Factors, and Type 2 Diabetes Among 550,000 Chinese Adults: Results from Two Independent Asian Cohorts

Abstract Background Genetics plays an important role in the development of type-2 diabetes (T2D). Polygenic risk scores (PRS) are increasingly used to quantify genetic risk of T2D in epidemiological studies. These scores, when integrated into analyses of modifiable lifestyle factors, may improve understanding of T2D etiology, as the strength of association with T2D and some lifestyle or demographic factors may vary according to genetic predisposition. Methods We examined PRS-lifestyle factor interactions on T2D with data from the United States Health and Retirement Study (HRS), a prospective longitudinal cohort of older adults (≥50 at baseline). HRS contains nationally representative samples of Black and White Americans with pre-calculated PRS for T2D (N = 14,001). Covariates included sex, education, BMI, smoking, alcohol, and physical activity. Predicted prevalence and incidence of T2D were calculated with logistic regression models. Nonparametric bootstrap method was performed to calculate differences in T2D prevalence and incidence by PRS percentiles and interaction variables. Results Significant interaction (p_interaction=0.0096) was detected between PRS and physical activity among Whites only. In those with the lowest decile of PRS, T2D prevalence was similar (∼10%) for those reporting no physical activity compared to low or moderate activity. In those with the top decile of PRS, lower T2D prevalence (17%, 95%CI:14.8,19.6) was observed among those with moderate compared to no activity (24%, 95%CI:20.4,27.5). Incident T2D in Whites followed a similar pattern (p_interaction=0.0194). Among Black participants, no significant interaction with any lifestyle variables was detected. Conclusions Interaction of different genetic risk profiles with lifestyle factors may inform understanding of why certain inventions are more or less effective in different groups of people, potentially improving clinical and prevention interventions. Key messages Protection conferred by physical activity on T2D varied by underlying genetic risk. Gene-environment interaction studies provide insights on why lifestyle factors vary in their associations with T2D.

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Genetic risk, adherence to a healthy lifestyle, and type 2 diabetes risk among 550,000 Chinese adults: results from 2 independent Asian cohorts

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz310 ◽

2020 ◽

Vol 111 (3) ◽

pp. 698-707 ◽

Cited By ~ 2

Author(s):

Haoxin Li ◽

Chiea-Chuen Khor ◽

Junning Fan ◽

Jun Lv ◽

Canqing Yu ◽

...

Keyword(s):

Type 2 Diabetes ◽

Genetic Risk ◽

Lower Risk ◽

Healthy Lifestyle ◽

Genetic Risk Score ◽

Lifestyle Factors ◽

Diabetes Risk ◽

Unhealthy Lifestyle ◽

High Genetic Risk

ABSTRACT Background Whether genetic susceptibility to type 2 diabetes is modified by a healthy lifestyle among Chinese remains unknown. Objectives The aim of the study was to determine whether genetic risk and adherence to a healthy lifestyle contribute independently to the risk of developing type 2 diabetes. Methods We defined a lifestyle score using BMI, alcohol intake, smoking, physical activities, and diets in 461,030 participants from the China Kadoorie Biobank and 38,434 participants from the Singapore Chinese Health Study. A genetic risk score was constructed based on type 2 diabetes loci among 100,175 and 16,172 participants in each cohort, respectively. A Cox proportional-hazards model was used to estimate the interaction between genetic and lifestyle factors on the risk of type 2 diabetes. Results In 2 independent Asian cohorts, we consistently found a healthy lifestyle (the bottom quintile of lifestyle score) was associated with a substantially lower risk of type 2 diabetes than an unhealthy lifestyle (the top quintile of lifestyle score) regardless of genetic risk. In those at a high genetic risk, the risk of type 2 diabetes was 57% lower among participants with a healthy lifestyle than among those with an unhealthy lifestyle in the pooled cohorts. Among participants at high genetic risk, the standardized 10-y incidence of type 2 diabetes was 7.11% in those with an unhealthy lifestyle vs. 2.45% in those with a healthy lifestyle. Conclusions In 2 independent cohorts involving 558,302 Chinese participants, we did not observe an interaction between genetics and lifestyle with type 2 diabetes risk, but our findings provide replicable evidence to show lifestyle factors and genetic factors were independently associated with the risk of type 2 diabetes. Within any genetic risk category, a healthy lifestyle was associated with a significantly lower risk of type 2 diabetes among the Chinese population.

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Dietary Fat Quality and Genetic Risk of Type 2 Diabetes

Diabetes ◽

10.2337/db18-21-or ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 21-OR

Author(s):

JORDI MERINO ◽

HASSAN S. DASHTI ◽

MARTA GUASCH ◽

CHRISTINA ELLERVIK ◽

CAREN SMITH ◽

...

Keyword(s):

Type 2 Diabetes ◽

Dietary Fat ◽

Genetic Risk ◽

Fat Quality

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1655-P: Genetic Risk Factors for Incident Cardiovascular Disease in Type 2 Diabetes Patients

Diabetes ◽

10.2337/db20-1655-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 1655-P

Author(s):

SOO HEON KWAK ◽

JOSEP M. MERCADER ◽

AARON LEONG ◽

BIANCA PORNEALA ◽

PEITAO WU ◽

...

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Genetic Risk ◽

Genetic Risk Factors ◽

Incident Cardiovascular Disease ◽

Diabetes Patients

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Menstrual Cycle Characteristics Across the Reproductive Lifespan, Lifestyle Factors and Risk of Type 2 Diabetes

SSRN Electronic Journal ◽

10.2139/ssrn.3564418 ◽

2020 ◽

Author(s):

Yi-Xin Wang ◽

Zhilei Shan ◽

Mariel Arvizu ◽

An Pan ◽

JoAnn E. Manson ◽

...

Keyword(s):

Type 2 Diabetes ◽

Menstrual Cycle ◽

Lifestyle Factors

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Analysis of rare coding variants in 200,000 exome‐sequenced subjects reveals novel genetic risk factors for type 2 diabetes

Diabetes/Metabolism Research and Reviews ◽

10.1002/dmrr.3482 ◽

2021 ◽

Author(s):

David Curtis

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Genetic Risk ◽

Genetic Risk Factors ◽

Coding Variants

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Interaction between dietary branched-chain amino acids and genetic risk score on the risk of type 2 diabetes in Chinese

Genes & Nutrition ◽

10.1186/s12263-021-00684-6 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Weiqi Wang ◽

Haiyang Jiang ◽

Ziwei Zhang ◽

Wei Duan ◽

Tianshu Han ◽

...

Keyword(s):

Type 2 Diabetes ◽

Genetic Predisposition ◽

Genetic Risk ◽

Odds Ratio ◽

Regression Models ◽

Fasting Glucose ◽

Genetic Risk Score ◽

Branched Chain Amino Acids ◽

Branched Chain

Abstract Background and objectives Previous studies have found the important gene-diet interactions on type 2 diabetes (T2D) incident but have not followed branched-chain amino acids (BCAAs), even though they have shown heterogeneous effectiveness in diabetes-related factors. So in this study, we aim to investigate whether dietary BCAAs interact with the genetic predisposition in relation to T2D risk and fasting glucose in Chinese adults. Methods In a case-control study nested in the Harbin Cohort Study on Diet, Nutrition and Chronic Non-Communicable Diseases, we obtained data for 434 incident T2D cases and 434 controls matched by age and sex. An unweighted genetic risk score (GRS) was calculated for 25 T2D-related single nucleotide polymorphisms by summation of the number of risk alleles for T2D. Multivariate logistic regression models and general linear regression models were used to assess the interaction between dietary BCAAs and GRS on T2D risk and fasting glucose. Results Significant interactions were found between GRS and dietary BCAAs on T2D risk and fasting glucose (p for interaction = 0.001 and 0.004, respectively). Comparing with low GRS, the odds ratio of T2D in high GRS were 2.98 (95% CI 1.54–5.76) among those with the highest tertile of total BCAA intake but were non-significant among those with the lowest intake, corresponding to 0.39 (0.12) mmol/L versus − 0.07 (0.10) mmol/L fasting glucose elevation per tertile. Viewed differently, comparing extreme tertiles of dietary BCAAs, the odds ratio (95% CIs) of T2D risk were 0.46 (0.22–0.95), 2.22 (1.15–4.31), and 2.90 (1.54–5.47) (fasting glucose elevation per tertile: − 0.23 (0.10), 0.18 (0.10), and 0.26 (0.13) mmol/L) among participants with low, intermediate, and high genetic risk, respectively. Conclusions This study indicated that dietary BCAAs could amplify the genetic association with T2D risk and fasting glucose. Moreover, higher BCAA intake showed positive association with T2D when genetic predisposition was also high but changed to negative when genetic predisposition was low.

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