Poveda Alaitz, Chen Yan, Brändström Anders, Engberg Elisabeth, Hallmans Göran, Johansson Ingegerd, Renström Frida, Kurbasic Azra, Franks Paul W
Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Clinical Research Centre, Lund University, Jan Waldenströms gata 35, Building 91, Skåne University Hospital, SE-20502, Malmö, Sweden.
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Bilbao, Spain.
Diabetologia. 2017 Mar;60(3):442-452. doi: 10.1007/s00125-016-4184-0. Epub 2016 Dec 21.
AIMS/HYPOTHESIS: Little is known about the heritable basis of gene-environment interactions in humans. We therefore screened multiple cardiometabolic traits to assess the probability that they are influenced by genotype-environment interactions.
Fourteen established environmental risk exposures and 11 cardiometabolic traits were analysed in the VIKING study, a cohort of 16,430 Swedish adults from 1682 extended pedigrees with available detailed genealogical, phenotypic and demographic information, using a maximum likelihood variance decomposition method in Sequential Oligogenic Linkage Analysis Routines software.
All cardiometabolic traits had statistically significant heritability estimates, with narrow-sense heritabilities (h ) ranging from 24% to 47%. Genotype-environment interactions were detected for age and sex (for the majority of traits), physical activity (for triacylglycerols, 2 h glucose and diastolic BP), smoking (for weight), alcohol intake (for weight, BMI and 2 h glucose) and diet pattern (for weight, BMI, glycaemic traits and systolic BP). Genotype-age interactions for weight and systolic BP, genotype-sex interactions for BMI and triacylglycerols and genotype-alcohol intake interactions for weight remained significant after multiple test correction.
CONCLUSIONS/INTERPRETATION: Age, sex and alcohol intake are likely to be major modifiers of genetic effects for a range of cardiometabolic traits. This information may prove valuable for studies that seek to identify specific loci that modify the effects of lifestyle in cardiometabolic disease.
目的/假设：人们对人类基因 - 环境相互作用的遗传基础知之甚少。因此，我们筛选了多种心脏代谢特征，以评估它们受基因型 - 环境相互作用影响的可能性。
在VIKING研究中分析了14种已确定的环境风险暴露因素和11种心脏代谢特征，该研究队列包括来自1682个扩展家系的16430名瑞典成年人，他们拥有详细的系谱、表型和人口统计学信息，使用顺序寡基因连锁分析程序软件中的最大似然方差分解方法进行分析。
所有心脏代谢特征均有统计学上显著的遗传力估计值，狭义遗传力（h²）范围为24%至47%。检测到年龄和性别（大多数特征）、身体活动（甘油三酯、2小时血糖和舒张压）、吸烟（体重）、酒精摄入量（体重、BMI和2小时血糖）和饮食模式（体重、BMI、血糖特征和收缩压）存在基因型 - 环境相互作用。经过多重检验校正后，体重和收缩压的基因型 - 年龄相互作用、BMI和甘油三酯的基因型 - 性别相互作用以及体重的基因型 - 酒精摄入量相互作用仍然显著。
结论/解读：年龄、性别和酒精摄入量可能是一系列心脏代谢特征遗传效应的主要调节因素。这些信息对于旨在识别影响心脏代谢疾病生活方式效应的特定基因座的研究可能具有重要价值。
