Table 1.
GxE genes and SNPs under selection for climatic and geographic characteristics
| Gene/SNP | Climate/Geography factor | Cardiometabolic GxE, phenotype-environmental factor |
|---|---|---|
|
ACE-rs7214530 |
Winter PC1 [58] |
SBP-physical activity; LC |
|
ADAMTS9 |
Hypoxia - high-altitude Amharans (Ethiopia) [61] |
LC |
|
ADH1C |
Digestion of milk and dairy products; metabolism of carbohydrates, starch, proteins, lipids and phosphates; alcohol metabolism [60] |
BMI-alcohol consumption; waist circumference-alcohol consumption |
|
ADRA2B-rs7604842 |
Summer PC1 [58] |
T2DM-physical activity; LC |
|
ANGPTL4 |
Hypoxia - high-altitude Tibetans [62] |
HDL-C-carbohydrate, percent energy from |
|
APOA4 - rs5110 |
Nutritional advantage to those with high milk consumption [63] |
Varirous GxEs: blood lipids-dietary fatty acid intake |
|
CD36 |
Dispersal and subsequent exposure to novel climates; summer PC1; fat consumption [58,60,64] |
LC |
|
CETP |
Dispersal and subsequent exposure to novel climates; energy metabolism and hot or cold tolerance; summer PC2 [58,60] |
Cholesterol, total-fat, total intake; Δcholesterol, total-SFA, percent energy from; HDL-C-diet (3); HDL-C-physical activity (4); HDL-C-alcohol consumption (2); HDL-C-fat, total, percent energy from; HDL-C-MUFA, percent energy from; HDL-C-SFA, percent energy from; triglyceride-alcohol consumption; LC |
|
CLOCK-rs1979605 |
Summer PC2 [58] |
BMI-physical activity; glucose, fasting-MUFA, percent energy from; insulin resistance (HOMA-IR)-MUFA, percent energy from; waist circumference-SFA, percent energy from |
|
CYP1A2 |
Domestication of plants [60] |
myocardial infarction-coffee intake |
|
CYP3A5 |
Domestication of plants; aridity (salt retention adaptation) in some Africans [60,65] |
DBP-sodium intake; SBP-sodium intake; LC |
|
EDNRA |
Hypoxia - high-altitude Tibetans [66] |
Arterial stiffness-physical activity |
|
FABP2-rs1799883 |
Latitude [58] |
ΔSBP-Mediterranean hypocaloric diet + exercise (MHD + E); Δglucose, fasting-MHD + E; ΔLDL-C-MHD + E; glucose tolerance-low-fat diet; glucose, fasting-low-fat diet; insulin, plasma, fasting-low-fat diet; LC |
|
FABP2 |
Dispersal and subsequent exposure to novel climates; latitude [58,60] |
(see above) |
|
GNPDA2 |
Precipitation; summer [59] |
Δbody weight-weight-loss intervention + exercise |
|
LEPR-rs1137100 |
Winter PC1 [58] |
SBP-physical activity; Δinsulin, fasting-physical activity |
|
LEPR |
Digestion of milk and dairy products; metabolism of carbohydrates, starch, proteins, lipids and phosphates; alcohol metabolism; energy metabolism, hot or cold tolerance; latitude, summer PC2; winter PC1 [58,60] |
Δbody weight-low-calorie diet; insulin resistance (HOMA-IR)-PUFA, N-3, plasma; insulin resistance (HOMA-IR)-PUFA, N-6, plasma; insulin, plasma, fasting-PUFA, N-3, plasma; insulin, plasma, fasting-PUFA, N-6, plasma; ΔSBP-MHD + E; ΔBMI-MHD + E; Δbody weight-MHD + E; Δwaist circumference-MHD + E; LC |
|
LCT |
Dairy farming and milk usage; dietary preferences; alcohol consumption [60] |
BMI-lactose; body weight-lactose; waist circumference-lactose |
|
LIPE |
Hypoxia - high-altitude Ethiopians [67] |
BMI-physical activity; cholesterol:HDL-C ratio-physical activity; LC |
|
LPA |
Dispersal and subsequent exposure to novel climates; winter PC2 [58,60] |
Lp (a), plasma-fish intake |
|
PON1-rs662 |
Summer PC1 [58] |
Cholesterol, total-smoking; HDL-C-physical activity; HDL-C-PUFA, N-9, oleic acid intake; LDL-C-smoking; triglyceride-smoking; LC |
|
PON1 |
Dispersal and subsequent exposure to novel climates; summer PC1 [58,60] |
(see above) |
|
PPARA |
Hypoxia - high-altitude Tibetans [62] |
CRP, plasma-PUFA, N-3, percent energy from; triglyceride-PUFA, N-3, percent energy from; triglyceride-PUFA, N-6, percent energy from; triglyceride-PUFA, percent energy from; waist circumference-fat, total intake; waist circumference-SFA intake; HDL-C-PUFA intake; LC |
|
PPARD |
Dairy farming and milk usage; dietary preferences; alcohol consumption [60] |
ΔHDL-C-physical activity; LDL particle size-PUFA:SFA ratio; ΔVO2max-physical activity; Δwork output, max-physical activity; LC |
|
PPARGC1A-rs4550905 |
Winter PC1 [58] |
BMI-alcohol consumption; BMI-physical activity; Δinsulin resistance (HOMA-IR)-low-calorie diet; LC |
|
TCF7L2-rs11196175 |
Summer PC1 [58] |
Glucose, fasting-fat, total, percent energy from; insulin resistance (HOMA-IR)-fat, total, percent energy from; insulin sensitivity-SFA, percent energy from; insulin, plasma, fasting-SFA, percent energy from; metabolic syndrome-SFA, percent energy from; LC |
|
UCP1-rs1800592 |
Temperature - cold resistance [68] |
ΔBMI-energy intake; Δbody weight-energy intake; Δwaist circumference-energy intake; LC |
|
UCP2-rs659366 |
Temperature - cold resistance [68] |
Δbody weight-high-calorie diet; ΔBMI-low-calorie diet; BMI-homestead; LC |
|
UCP3-rs1800849 |
Temperature - cold resistance [68] |
BMI-physical activity |
| UCP3 | Dispersal and subsequent exposure to novel climates; winter PC1; temperature - cold resistance [58,60] | Δbody weight-high-calorie diet |
When no SNP is listed, only the gene itself was shown to be under selection.
bold = phenotype-environment pair found in (n) studies.
LC = selected GxEs based less common phenotypes or environmental factors can be found in (Additional file 1).
Δ refers to a change in the phenotype, typically after an intervention.