Table 5 Significant gene-phenotype associations from rare variant burden analysis

DNAJC22

rs748318571; c.572C>T; p.Ala191Val

Glucose

10.80

69.9

5.95E−17

1

6041|3|1

eQTL in NDDM mice model nearby DNAJC22 homologous gene

-

HLF

–; c.465G>T; p.Pro155=

HBA1c

− 10.26

68.2

1.45E−16

1

6041|3|1

-

-

LGI3

rs149352514; c.1150G>A; p.Gly384Ser

BMI

16.34

56.1

6.62E−14

1

6037|7|1

LGI3 may be a candidate adipokine that is perturbed in obesity and suppresses adipogenesis through its receptor, ADAM23

70

ITPK1

–; c.1111C>T; p.Pro371Ser

ALT-GPT

20.63

50.6

1.12E−12

2

6012|31|2

-

-

rs567443586; c.1074C>A; p.Ser358Arg

MARCH10

–; c.2026G>C; p.Pro676Ala

Glucose

7.25

44.3

2.70E−11

4

5854|182|9

-

-

rs116835087; c.1759G>A; p.Gly587Ser

rs60472825; c.1285C>T; p.His429Tyr

rs529095649; c.113A>G; p.Tyr38Cys

DNAJC15

rs144620914; c.383-2A>G; –

ALT-GPT

43.58

43.5

4.20E−11

1

6039|5|1

Silencing hepatic MCJ attenuates non-alcoholic fatty liver disease (NAFLD) by increasing mitochondrial fatty acid oxidation (reduced NAFLD liver steatosis and fibrosis in MCJ deficient mice)

72

RPS6KA3

rs1026040538; c.28C>T; p.Arg10Cys

Sex hormone-binding globulin

130.50

42.1

8.25E−11

1

6040|4|1

Same gene-phenotype association identified in a dataset from UK biobank

73

FMR1NB

rs782656279; c.35A>G; p.Asn12Ser

Ferritin

223.39

39.1

3.95E−10

3

6041|1|3

Gene encodes ferritin heavy chain 1 pseudogene 8

-

rs782029879; c.172C>T; p.Arg58Trp

–; c.536A>C; p.Asp179Ala

RGCC

; c.19C>T; p.Gln7^a

total cholesterol

− 2.57

37.6

8.56E−10

1

6034|10|1

RGD: association in rats with serum cholesterol

74

STK32C

rs377335124; c.486C>T; p.Asp175=

BMI

7.78

35.5

2.44E−09

2

6023|20|2

-

-

rs564621303; c.302-4_302-1dup; –

HHAT

rs757118759; c.62G>C; pArg21Pro

ALT-GPT

26.95

33.8

5.81E−09

2

6032|11|2

-

-

rs149597734; c.1112C>T; p.Thr371Ile

PAX2

rs199876625; c.453G>A; p.Pro182=

LDL cholesterol

− 2.17

33.2

8.14E−09

1

6027|17|1

-

-

TFR2

rs1002859413; c.554G>A; p.Arg185His

Glucose

2.77

33.2

8.22E−09

1

6018|26|1

An association with hereditary hemochromatosis type III, a condition with complications that result in pancreatic damage and secondary diabetes

72