Table 1 Multiple published functional and association studies link genes identified by SWIF(r) to metabolism-related and obesity-related phenotypes

From: Localization of adaptive variants in human genomes using averaged one-dependence estimation

Gene

SNP(s)

DAF

P (sweep)

Studies relating gene to metabolism-obesity phenotype

Refs.

DNM3

rs12121064

54%

70%

Associated with waist–hip ratio in Europeans (rs1011731, GWA p = 7.5 × 10−9)

73

    

Associated with waist circumference in Hispanic women (GWA replication p = 1.5 × 10−3)

74

    

Associated with weight loss after gastric bypass surgery

75

ESRRG

rs11808388

62%

99.2%

Regulates adipocyte differentiation by modulating the expression of adipogenesis-related genes

76

    

Candidate obesity-susceptibility gene based on epigenetic profile and association with BMI

77

    

May be involved in increasing the potential for energy expenditure in brown adipocytes

78

    

Mediates hepatic gluconeogenesis

79

    

Contributes toward maintenance of hepatic glucose homeostasis

80

    

Necessary for metabolic maturation of pancreatic β-cells

81

    

Significantly up-regulated under treatment with cholesterol drug fenofibrate

82

TTN

rs16866534

44%

76%

Isoform composition in cardiac tissue is regulated by insulin signaling, possibly contributing to altered diastolic function in diabetic cardiomyopathy

83

MYH15

rs3957559

49%

76%

Variant rs3900940, along with four other variants, contributes to elevated risk for coronary heart disease

84

ADIPOQ

rs6444174

56%

90%

rs6444174 associated with adiponectin levels in African-American women

37

    

Associated with plasma adiponectin levels in Europeans (rs17366568, GWA p = 4.3Ă—10−24)

85, 86

    

Associated with plasma adiponectin levels in African Americans (rs4686807, GWA p = 1.6 × 10−11)

87

    

Associated with plasma adiponectin levels in East Asians (rs822391, GWA p = 1.6 × 10−10)

87

    

Associated with coronary heart disease, BMI, childhood obesity, metabolic syndrome, and type II diabetes

37, 88,89,90,91,– 92

    

Serum adiponectin levels are associated with metabolic health and cardiovascular risk

93, 94

PDGFRA

rs4530695

64%

75%

Used in molecular biology as a marker for white adipocytes

95

    

Controls pancreatic β-cell proliferation

96

    

Plays a role in the link between obesity and inhibited placental development

97

ASTN2

rs16934033

50%

76%

Contributes to genetic variation of plasma triglyceride concentrations

98

    

marginally associated with childhood obesity in Hispanic individuals (GWA p = 2.4 × 10−6)

99

SIDT2

rs11605217

27%

57%

Important regulator of insulin secretion

100

    

Mice without the gene are glucose intolerant and have decreased serum insulin

101, 102

    

Associated with triglyceride levels (rs1242229, GWA p = 3.1Ă—10−20)

103

RASSF8

rs16929850

61%

95.3%

Expression is significantly altered by fasting in mice

104

 

rs16929965

64%

99.9%

  
 

rs2729646

68%

98.4%

  
 

rs956627

64%

99.9%

  

DUT

rs11637235

33%

76%

Missense variant causes a syndrome characterized in part by early onset diabetes mellitus

105

PEPD

rs12975240

62%

76%

Associated with adiponectin levels in multiple populations (rs731839, rs4805885, rs8182584, rs889139, rs889140, GWA p values between 1.1 × 10−9 and 2.2 × 10−13)

87, 106

    

Associated with type II diabetes (rs3786897, GWA p = 1.3 × 10−9)

107

    

Associated with fasting insulin levels (rs731839, GWA p = 5.1 × 10−12)

108

    

Associated with serum lipid levels

109

    

Expression is modulated by n-3 fatty acids

110

PHACTR3

rs1182507

54%

76%

Regulation in adipose tissue is BMI-dependent

38

    

Candidate obesity gene based on epigenetic profile

77

  1. The second column contains all variants within the genes listed that have posterior sweep probability ≥50% as calculated by SWIF(r). Column 3 shows the DAF in the ‡Khomani San at the SNP in column 2, and column 4 shows the calibrated posterior sweep probability calculated by SWIF(r) at that site. For GWA studies, GWA p values are given for the strongest SNP associations. Bold rsid indicates a result about the specific SNP identified by SWIF(r) in column 2. All genes highlighted in Fig. 3b are included in this table except MCC and MLIP, for which additional associations to metabolism-related and obesity-related phenotypes could not be found beyond the dbGaP categories in Fig. 3c
  2. BMI, body mass index; DFA, derived allele frequency; GWA, genome-wide association; SNP, single-nucleotide polymorphism; SWIF(r), SWeep Inference Framework (controlling for correlation)
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