Table 3 Top candidate genes for alcoholism

From: Genetic risk prediction and neurobiological understanding of alcoholism

Gene

symbol/name

Discovery GWAS1

best P-value SNP

Internal score nominally significant SNPs/total SNPs tested (% significant)

Human genetic evide nce

Human post-mortem brain expression evidence

Human

peripheral expression evidence

Animal model genetic evidence

Animal model brain expression evidence

Animal model peripheral (blood) expression evidence

CFG

score

DBP

stress 4

DBP

stress

DHA 5

SNCA, synuclein alpha (non A4 component of amyloid precursor)

0.02363 rs17015982

2

4/68 (5.89%)

Association7,8

(D)

PFC8, 9, 10

(I)

FC11

(I) Blood12

(I) Blood13

(I) Serum14

DNA hypermethylation15

QTL16

(D)

FC, CP17

(I)

HIP P1

AMY P33

(I) Blood male adult cynomolgus monkeys18

13

(D)

AMY,

blood

(I) Blood

GFAP, glial fibrillary acidic protein

0.01052 rs744281

3

4/12 (33.34%)

Linkage19

(D)

FC9,11,20

  

(I)

FC21

HIP, NAC, PFC P13

 

9.5

(I)

AMY

 

DRD2, dopamine receptor D2

0.03652 rs4938019

2

2/46 (4.35%)

Association22, 23, 24, 25, 26

(D)

FC, CP27

(D)28

 

(Transgenic) alcohol aversion decreased alcohol consumption29

  

9

(D)

PFC

(I) AMY

GRM3,

glutamate receptor, metabotropic 3

0.001126

rs41440

2

15/133

(11.28%)

Linkage30,31

(D)

HIP32

  

(I)

NAC33

(D)

FC34

(D)

CP P23

 

9

(I)

AMY

 

MBP, myelin basic protein

0.006503 rs1124941

2

16/109 (14.68%)

 

(D)

FC11

  

(I)

PFC35

(D)

cerebellum36

delayed expression37

(D) CG-4 glial cells rat brain38

8.5

(D)

PFC

(I)

AMY

(D) Blood

(I) HIP

MOBP, myelin-associated oligodendrocyte basic protein

0.01231 rs562545

2

2/43 (4.66%)

 

(D)

FC11

 

QTL39

(I)

PFC35

(D)

NAC40

(I) whole brain41

(I)

PFC P13

 

8.5

(D)

PFC

(I)

AMY

(D) Blood

(I) HIP

GNAI1,

guanine nucleotide binding protein (G protein), alpha-inhibiting activity polypeptide 1

0.00059

rs12706724

2

11/66

(16.67%)

Linkage42,43

(D)

HIP32

  

(D)

NAC P33

 

8

(D)

PFC

 

MOG, myelin oligodendrocyte glycoprotein

0.01429 rs3117292

2

3/19 (15.79%)

 

(D)

FC, HIP11,32

  

(D)

VTA44

(I)

PFC35

(I) PFC P13

 

8

(D)

PFC

(I) HIP

RXRG, retinoid X receptor, gamma

0.005815 rs10800098

2

1/37 (2.71%)

Linkage45

(D)

FC11

  

(I) CP P33

 

8

(D)

PFC

 

SYT1, synaptotagmin I

0.04139 rs1245810

2

7/117 (5.99%)

 

(D)

NAC46

  

(D)

FC34

(D)

HIP47

(I)

Cultured neurons48

(I) Cortical neurons49

8

(D)

PFC

(D)

AMY

TIMP2, TIMP metallopeptidase inhibitor 2

0.04309 rs7502935

2

1/25 (4%)

Linkage45

(D)

FC, HIP, NAC32,46,50

  

(I)

VTA44

 

8

(D)

PFC

(D)

Blood

  1. Abbreviations: AMY, amygdala; Association, association evidence; CFG, convergent functional genomics; CP, caudate–putamen; D, decreased in expression; DBP, D-box-binding protein; DHA, docosahexaenoic acid; GWAS, genome-wide association study; HIP, hippocampus; I, increased; Linkage, linkage evidence; NAC, nucleus accumbens; P1, paradigm 1; P2, Paradigm 2; P3, paradigm 3 in the Rodd et al;3 PFC, prefrontal cortex; QTL, quantitative trait loci; SNP, single-nucleotide length polymorphism; TG, transgenic; VT, ventral tegmentum; VTA, ventral tegmental area.
  2. Top genes with a CFG score of 8 and above that overlapped with top genes from the stress-reactive animal model are shown (n=11; Figure 4). Best P-value SNP within the gene or flanking regions is depicted. A more complete list of genes with CFG score of 8 and above (n=135) is available in the Supplementary Information section (Supplementary Table S1). Underlined gene symbol represents means gene is a blood biomarker candidate. Bold P-values <0.001.
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