Table 3.
Chr | Marker (Position/cM) |
LOD | Number of Genes in Region (~±1 LOD) & Candidate Gene Examples |
Independent Linkage Results in Humans |
---|---|---|---|---|
1 1 |
D1S2667 (29.9) D1S2697 (38.3) |
2.104 2.189 |
Total genes in region = 497 with 49 being ethanol-related*, including: STX12 (syntaxin 12-binding protein) (Rodd et al., 2006) 1p35.3; separates for ethanol preference in rats (Treadwell, 2006) and down-regulated in alcoholic vs. control human brains (Sokolov et al., 2003). OPRD1 (opioid receptor, delta-1) 1p36.1-p34.3; reported to modulate substance dependence risk , but null findings also reported (Xuei et al., 2007; Zhang et al., 2008). |
De Andrade et al. (2005): LOD=2.15 @ 52 cM for maximum number of drinks in 24 hours. |
1 | D1S218 (189.2) | 2.136 | Total genes in region = 238 with 33 being ethanol-related*, including: DHX9 (DEAH (Asp-Glu-Ala-His) box polypeptide 9) 1q25: down-regulated in the temporal cortex of alcohol abuse indivudals versus controls (Sokolov et al., 2003). |
Hill et al (2004): LOD=3.46 @ 169 cM (D1S196) for alcoholism. |
1 | GATA88F03 (227.3) | 2.803 | Total genes in region = 237 with 20 being ethanol-related*, including: AGT (angiotensinogen) 1q42.2; may mediate alcohol consumption as precursor of angiotensin II, which correlates with voluntary alcohol intake in mice (Maul et al., 2001); baseline levels are higher in prefrontal cortex of alcohol-preferring vs. non- alcohol preferring rats (Rodd et al., 2006); down-regulated in frontal cortex of alcoholic vs. control human brains (Lewohl et al., 2000). |
Agrawal et al. (2007): LOD=2.0 @ 213 cM for DSM-IV alcohol dependence symptoms. Dick et al. (2002): LOD=2.3 @ 235 cM for a factor age of onset of regular drinking and harm avoidance. |
3 | D3S1267 (131.8) | 2.682 | Total genes in region = 187 with 11 being ethanol-related*, including: TRH (thyrotropin-releasing hormone) 3q13.3-q21; In mice, thyrotropin-releasing hormone appears to modulate various parameters related to ethyl alcohol consumption (e.g. French et al., 1993) . |
Ma et al. (2005): LODs up to 1.3 @ ~130 cM (3p21) for alcohol dependence. Ehlers et al. (2005): LOD=2.2 @ 143 cM for alcohol craving. |
3 | GATA92B06 (177.4) AAC030 (186.9) |
2.503 2.011 |
Total genes in region = 187 with 10 being ethanol-related*, including: SOX2 (SRY (sex determining region Y) – box 2) 3q26.3-q27; up-regulated in the prefrontal cortex of alcoholic versus control subjects (Iwamoto et al., 2004). |
|
5 | GATA141B10 (82.5) | 2.498 | Total genes in region = 169 with 52 being ethanol-related*, including: PIK3R1 (phosphoinositide-3-kinase, regulatory subunit 1 (alpha)) 5q13.1; associated with patterns of risky alcohol consumption in male adolescents (Desrivieres et al., 2008). CARTPT (cocaine- and amphetamine-regulated transcript (CART) prepropeptide) 5q13.2; associated with alcoholism in Korean males (Jung et al., 2004). |
Hill et al (2004): LOD=3.54 @ 108 cM (D5S644) for alcoholism. |
6 6 6 6 |
ATA109H09 (8.7) D6S1574 (14.4) SE30 (15.1) D6S309 (19.3) |
2.296 2.178 3.265 2.220 |
Total genes in region = 80 with 23 being ethanol-related*, including: NRN1 (neuritin 1) (Rodd et al., 2006) 6p25.1; implicated in the development of schizophrenia (Moises et al., 2002) and differential expression profiles for bipolar (Jurata et al., 2004); cross-matched with alcoholism due to clinical comorbidity that may in part be due to genetic overlap (Nurnberger Jr. et al., 2004). |
Hill et al (2004): LOD=4.25 @ 15 cM (D6S1574) for alcoholism. Ma et al. (2005): LODs up to 1.57 @ 6p24 for definitions of alcohol dependence. |
20 20 |
AAAT007 (2.4) D20S889 (11.1) |
2.399 2.358 |
Total genes in region = 91 with 7 being ethanol-related*, including: PDYN (prodynorphin) 20pter-p12; associated with risk for alcohol dependence (Xuei et al., 2006) and cocaine/alcohol codependence (Williams et al., 2007). |
|
X | DXS6800 (88.2) | 2.050 | Total genes in region = 230 with 15 being ethanol-related*, including: ITGB1BP2 (integrin beta 1 binding protein (melusin) 2) Xq12-q13.1; down- regulated in the nucleus accumbens, a brain region thought to mediate the rewarding effects of addictive substances, in alcoholics versus controls (Flatscher-Bader et al., 2005). |
as listed at ERGR (Ethanol-Related Gene Resource - http://bioinfo.vipbg.vcu.edu/ERGR)