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Background: Some persons are genetically resistant to obesity, but only a few studies have evaluated thinness genes for preventing obesity. We aimed to investigate the association of polygenic variants with being underweight and their interaction with the lifestyles of middle‐aged and elderly persons and identify potential new genetic approaches for managing body weight. Methods: In total, 58,701 participants aged 40–77 years were recruited from urban hospitals in Korea. Underweight (case) was defined as body mass index (BMI) < 18.5 kg m2 (n = 991) and normal weight (control, n = 21,921) was defined as 18.5 ≤ BMI < 23 kg m2. A genome‐wide association study was run to identify thinness‐related single nucleotide polymorphisms (SNPs) after adjustment for compound factors using Gplink. The generalised multifactor dimensionality reduction program was used to identify the genetic variants with SNP–SNP interactions. The polygenic risk score (PRS) was calculated by summing up the number of risk alleles in each SNP and classifying them into low‐, medium‐ and high‐PRS. Results: The best model included the ANK2_rs7656666, CAST_rs28042, SLC1A3_rs928431867, CHST12_rs2906173, ALOX5_rs1051713, RGS6_rs17180754, ST8SIA5_rs79491311 and DCC_rs35721894 alleles. The participants with high‐PRS had a lower BMI (p < 0.0001) than those with low‐PRS and were 3.834 (2.58–5.70) times more likely to be underweight after multivariate adjustment (p < 0.001). The selected SNPs were correlated with each other and highly expressed in brain‐related genes. The genes with minor alleles of CAST_rs28042 and CHST12_rs2906173 exhibited a higher expression frequency in brain‐related tissues. PRS had significant interactions with protein, sodium, indigestible carbohydrates, calcium intake and exercise (p < 0.05), influencing the underweight state. People with a high‐PRS were more underweight than those with low‐PRS under high protein, sodium, high calcium, low indigestible carbohydrate intake and low exercise by 3.75, 3.88, 7.05, 3.18 and 3.80 times, respectively (p < 0.0001). Conclusions: In conclusion, adults having a high‐PRS were significantly correlated with being underweight, especially in combination with a particular nutritional status. These results show the potential for thinness genes to be applied to personalised nutrition for preventing obesity through targeted gene therapy. Highlights: There is less research on understanding the role of genetic mutations in maintaining underweight. The present study found that high‐risk scores of thinness‐related polygenic variants (PRS) were positively associated with being underweight by 3.83 times. PRS interacted with environmental factors, including protein, indigestible carbohydrates, sodium and calcium intake, as well as physical activity. The study clearly suggests that the discovery of single nucleotide polymorphism (SNP)–environment interactions by using PRS was notable for its influence on the state of being underweight. Therapies targeting these genes and the SNPs of PRS could help scientists prevent obesity and manage weight in the future. [ABSTRACT FROM AUTHOR]

We hypothesized that the haplotype of Bcl-2 genetic variants increases breast cancer risk and interacts with lifestyles in Korean women. We identified single nucleotide polymorphism (SNPs) of Bcl-2 associated with breast cancer risk after adjusting for covariates in 390 breast cancer patients and 36,726 women without any cancer that participated in the Korean Genomic Epidemiology Study (KoGES). An allelic genetic model showed that three SNPs (rs1944420, rs7236090, and rs2849382) in the Bcl-2 gene were significantly associated with breast cancer (ORs = 1.28, 0.84, and 0.79, respectively). The participants with the minor allele of the haplotype with three SNPs had 1.65-fold higher breast cancer risk than those with the major allele, after adjusting for covariates. Serum C-reactive protein concentration had a positive association with breast cancer risk. A significant interaction was also observed between the minor allele of the Bcl-2 haplotype and coffee intake (P = 0.03). A low coffee intake in women with the minor allele presented a higher breast cancer risk than a low coffee intake in those with the major allele. In conclusion, the risk of breast cancer risk was higher in post-menopausal women with the minor allele of the Bcl-2 haplotype, and consuming more than 1 cup of coffee per day reduced the risk. The results of this study could be applied to reduce the risk of breast cancer. [ABSTRACT FROM AUTHOR]

We hypothesized that subjects with genetic variants that increase sweet taste preference would consume more sucrose‐containing foods and have altered energy and glucose metabolisms, which would have interactions with lifestyles. Korean genome and epidemiology study (KoGES) was conducted to determine genetic variants and lifestyles including nutrient intakes by the Korean Center for Disease and Control during 2004–2013. Subjects were 8,842 adults aged 40–69 years in Ansan/Ansung cohorts in Korea. The associations between genetic risk scores(GRS) selected for influencing higher sweet preference and energy and glucose metabolism were examined using logistic regression after adjusting for covariates. GRS included 8 SNPs, TAS1R2_rs61761364, SLC2A5_rs11121306, SLC2A7_ rs769902, SLC2A5_rs765618, TRPM5_rs1965606, TRPV1_rs224495, TRPV1_ rs8065080, and TRPV1_rs8078502. Sweet taste preference was higher by 1.30‐folds in high GRS than in low GRS (p <.0001). Consistent with sweet taste preference, carriers with high GRS had a higher intake of sucrose‐containing foods by 1.25 (1.08–1.46)‐fold than those with low GRS after adjusting age, gender, BMI, and energy intake. However, glucose intolerance risk was rather lower by 0.861 (0.76–0.98)‐fold in high GRS than low GRS (p <.05). GRS tended to interact with mental stress to affect sucrose intake (p =.048). Only in low mental stress levels, sucrose‐containing food intake was higher in high GRS than low GRS. There was an interaction of GRS with physical activity to influence glucose intolerance. Serum glucose concentrations were lower by 0.808‐folds in high GRS than low GRS only in a high physical activity state. In conclusion, adults with genetically high sweet taste preference had a positive association with high sucrose‐containing food intakes and improved glucose tolerance. The genetic impact on sweetness preference was associated with offset by high mental stress and lack of physical activity. [ABSTRACT FROM AUTHOR]

Background and aims: Subcutaneous fat mass is negatively correlated with atherogenic risk factors, but its putative benefits remain controversial. We hypothesized that genetic variants that influence subcutaneous fat mass would modulate lipid and glucose metabolism and have interactions with lifestyles in Korean middle-aged adults with high visceral fat. Materials and methods: Subcutaneous fat mass was categorized by dividing the average of subscapular skin-fold thickness by BMI and its cutoff point was 1.2. Waist circumferences were used for representing visceral fat mass with Asian cutoff points. GWAS of subjects aged 40–65 years with high visceral fat (n = 3303) were conducted and the best gene-gene interactions from the genetic variants related to subcutaneous fat were selected and explored using the generalized multifactor dimensionality reduction. Genetic risk scores (GRS) were calculated by weighted GRS that was divided into low, medium and high groups. Results: Subjects with high subcutaneous fat did not have dyslipidemia compared with those with low subcutaneous fat, although both subject groups had similar amounts of total fat. The best model to influence subcutaneous fat included IL17A_rs4711998, ADCY2_rs326149, ESRRG_rs4846514, CYFIP2_rs733730, TCF7L2_rs7917983, ZNF766_rs41497444 and TGFBR3_rs7526590. The odds ratio (OR) for increasing subcutaneous fat was higher by 2.232 folds in the high-GRS group, after adjusting for covariates. However, total and LDL cholesterol, triglyceride and C-reactive protein concentrations in the circulation were not associated with GRS. Subjects with high-GRS had higher serum HDL cholesterol levels than those with low-GRS. Physical activity and GRS had an interaction with subcutaneous fat. In subjects with low physical activity, the odds ratio for high subcutaneous fat increased by 2.232, but subcutaneous fat deposition was not affected in the high-GRS group with high physical activity. Conclusion: Obese adults with high-GRS had more subcutaneous fat, but they did not show more dyslipidemia and inflammation compared to low-GRS. High physical activity prevented subcutaneous fat deposition in subjects with high GRS for subcutaneous fat. [ABSTRACT FROM AUTHOR]

Background: Since alcohol intake increases the prevalence of type 2 diabetes (T2DM) in Koreans, we tested the hypothesis that the interactions of genetic variants involved in β‐cell function and mass with alcohol intake increase the T2DM risk. Methods: The single nucleotide polymorphisms (SNPs) were selected by genome‐wide association study for insulin secretion after adjusting for age, gender, area of residence, body mass index, and alcohol intake (p < 1 × 10−4) in 8,842 middle‐aged adults in the Ansan/Ansung cohort. Genetic risk scores (GRSs) were calculated by summing the risk alleles of 4 selected SNPs, CDKAL1 rs7754840 and rs9460546, HHEX rs5015480, and OAS3 rs2072134. The GRSs were categorized into 3 groups by tertiles, and the association between GRS and insulin secretion was measured using logistic regression after adjusting for confounding factors in the Ansan/Ansung cohort. The results were confirmed by the Rural cohort. Results: HOMA‐IR was higher and HOMA‐B was much lower in the High‐GRS than the Low‐GRS in both cohorts. T2DM risk was higher by approximately 1.5‐fold in the High‐GRS than in the Low‐GRS in both cohorts. In the High‐GRS group, HOMA‐B decreased by 0.89‐ and 0.62‐fold in comparison with the Low‐GRS in the Ansan/Ansung cohort and Rural cohort. The GRS interacted with alcohol intake to increase the risk of developing T2DM in the Ansan/Ansung cohort (p = 0.036) and Rural cohort (p = 0.071). The risk of T2DM increased in the High‐GRS group with high alcohol intake and it was associated with decreased HOMA‐B. High alcohol intake decreased HOMA‐B regardless of GRS, and HOMA‐B was lower in the descending order of Medium‐GRS, Low‐GRS, and High‐GRS. However, HOMA‐IR was not altered by alcohol intake, but was elevated in the High‐GRS more than in the other groups. Conclusions: Subjects with a High‐GRS had an elevated risk of T2DM even with moderate alcohol intakes due to lower HOMA‐B. High alcohol intake appears to be a risk factor for all Asians regardless of alcohol intake. This research evaluated the effects of a high genetic risk score (GRS) for low insulin secretory capacity and alcohol consumption on the risk of developing type 2 diabetes (T2DM). High alcohol intake and a high GRS resulted in a much greater risk for T2DM. However, subjects with a High‐GRS had an elevated risk of T2DM even with moderate alcohol intake due to lower HOMA‐B. High alcohol intake appears to be a risk factor for all Asians regardless of GRS. [ABSTRACT FROM AUTHOR]