Adaptive genetic variation and heart disease risk.
OBJECTIVE
Obesity, dyslipidemia and cardiovascular disease are complex and determined by both genetic and environmental factors and their inter-relationships. Many associations from genome-wide association studies and candidate gene approaches have described a multitude of polymorphisms associating with lipid and obesity phenotypes but identified genetic variants account for only a small fraction of phenotypic variation.


RESULTS
That many genotype-phenotype associations involve variants under positive selection and that those variants respond to environmental cues together suggest prominent roles for both genetic adaptation and their interactions with the environment. Adaptive genetic variations interacting with environment modulate disease susceptibility but the level to which those variants contribute to dyslipidemia and obesity and how environmental factors, especially diet, alter the genetic association is not yet completely known.


CONCLUSIONS
It is evident that genetic variants under positive selection make important contributions to obesity and heart disease risk. Advances in resequencing the entire human genome will enable accurate identification of adaptive variants. Considering interactions between environmental factors and genotypes will empower both genome-wide association studies and characterization of the relationship between positive selection and the obese and dyslipidemic conditions.
Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA.
Laurence D
LD
Parnell
Yu-Chi
YC
Lee
Chao-Qiang
CQ
Lai
D000222:Adaptation, Physiological / Q000235:genetics*; D004032:Diet; D050171:Dyslipidemias / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006331:Heart Diseases / Q000235:genetics*; D006801:Humans; D009765:Obesity / Q000235:genetics