Positive Selection on Loci Associated with Drug and Alcohol Dependence.
paper
Primary
Public
- Authors
- Sadler, Brooke; Haller, Gabe; Edenberg, Howard; Tischfield, Jay; Brooks, Andy; Kramer, John; Schuckit, Marc; Nurnberger, John; Goate, Alison
- Year
- 2015
- Journal
- PloS one
- PMID
- 26270548
- DOI
- 10.1371/journal.pone.0134393
- PMCID
- PMC4536217
Much of the evolution of human behavior remains a mystery, including how certain disadvantageous behaviors are so prevalent. Nicotine addiction is one such phenotype. Several loci have been implicated in nicotine related phenotypes including the nicotinic receptor gene clusters (CHRNs) on chromosomes 8 and 15. Here we use 1000 Genomes sequence data from 3 populations (Africans, Asians and Europeans) to examine whether natural selection has occurred at these loci. We used Tajima's D and the integrated haplotype score (iHS) to test for evidence of natural selection. Our results provide evidence for strong selection in the nicotinic receptor gene cluster on chromosome 8, previously found to be significantly associated with both nicotine and cocaine dependence, as well as evidence selection acting on the region containing the CHRNA5 nicotinic receptor gene on chromosome 15, that is genome wide significant for risk for nicotine dependence. To examine the possibility that this selection is related to memory and learning, we utilized genetic data from the Collaborative Studies on the Genetics of Alcoholism (COGA) to test variants within these regions with three tests of memory and learning, the Wechsler Adult Intelligence Scale (WAIS) Block Design, WAIS Digit Symbol and WAIS Information tests. Of the 17 SNPs genotyped in COGA in this region, we find one significantly associated with WAIS digit symbol test results. This test captures aspects of reaction time and memory, suggesting that a phenotype relating to memory and learning may have been the driving force behind selection at these loci. This study could begin to explain why these seemingly deleterious SNPs are present at their current frequencies.
Tajima’s D and iHS Results.A-CTajima’s D andD-F) iHS for the LCT region on chromosome 2, the CHRNA3-B4-A5 gene cluster on chromosome 15 and the CHRNB3-A6 gene cluster on chromosome 8 across individuals of European (red), African (Purple) or Asian (green) ancestry. Lines are the 95% confidence intervals as calculated by permutation for iHS and Tajima’s D.
1–20 of 49
Next →
No entities extracted from this document yet.
No uploaded files.
Not in any collection.
| Citation | PMID | DOI | Status |
|---|---|---|---|
| Ashley-KochA, YangQ, OlneyRS (2000) Sickle hemoglobin (HbS) allele and sickle cell disease: a HuGE review. Am J Epidemiol 151: 839–845. 1079155710.1093/oxfordjournals.aje.a010288 | — | — | — |
| BerrettiniW, YuanX, TozziF, SongK, FrancksC, et al (2008) Alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking. Mol Psychiatry 13: 368–373. 10.1038/sj.mp.4002154 18227835PMC2507863 | — | — | — |
| BierutLJ (2009) Nicotine dependence and genetic variation in the nicotinic receptors. Drug Alcohol Depend 104 Suppl 1: S64–69. 10.1016/j.drugalcdep.2009.06.003 19596527PMC2748747 | — | — | — |
| BierutLJ, MaddenPA, BreslauN, JohnsonEO, HatsukamiD, et al (2007) Novel genes identified in a high-density genome wide association study for nicotine dependence. Hum Mol Genet 16: 24–35. 1715818810.1093/hmg/ddl441PMC2278047 | — | — | — |
| BierutLJ, StitzelJA, WangJC, HinrichsAL, GruczaRA, et al (2008) Variants in nicotinic receptors and risk for nicotine dependence. Am J Psychiatry 165: 1163–1171. 10.1176/appi.ajp.2008.07111711 18519524PMC2574742 | — | — | — |
| ChenMH, YangQ (2010) GWAF: an R package for genome-wide association analyses with family data. Bioinformatics 26: 580–581. 10.1093/bioinformatics/btp710 20040588PMC2852219 | — | — | — |
| DelaneauO, MarchiniJ, ZaguryJF (2012) A linear complexity phasing method for thousands of genomes. Nat Methods 9: 179–181.10.1038/nmeth.178522138821 | — | — | — |
| DragoJ, McCollCD, HorneMK, FinkelsteinDI, RossSA (2003) Neuronal nicotinic receptors: insights gained from gene knockout and knockin mutant mice. Cell Mol Life Sci 60: 1267–1280. 1294321710.1007/s00018-003-2259-9PMC11146083 | — | — | — |
| GarrettB, DubeS., TrosclairA., CaraballoR., & PechacekT. (2009) Cigarette Smoking—United States, 1965–2008. CDC Morbidity and Mortality Weekly Report 60: 109–113. | — | — | — |
| GarriganD, HammerMF (2006) Reconstructing human origins in the genomic era. Nat Rev Genet 7: 669–680. 1692134510.1038/nrg1941 | — | — | — |
| GottiC, MorettiM, GaimarriA, ZanardiA, ClementiF, et al (2007) Heterogeneity and complexity of native brain nicotinic receptors. Biochem Pharmacol 74: 1102–1111. 1759758610.1016/j.bcp.2007.05.023 | — | — | — |
| GruczaRA, WangJC, StitzelJA, HinrichsAL, SacconeSF, et al (2008) A risk allele for nicotine dependence in CHRNA5 is a protective allele for cocaine dependence. Biol Psychiatry 64: 922–929. 10.1016/j.biopsych.2008.04.018 18519132PMC2582594 | — | — | — |
| HallerG, KapoorM, BuddeJ, XueiX, EdenbergH, et al (2013) Rare missense variants in CHRNB3 and CHRNA3 are associated with risk of alcohol and cocaine dependence. Hum Mol Genet.10.1093/hmg/ddt463PMC388826324057674 | — | — | — |
| HoyleE, GennRF, FernandesC, StolermanIP (2006) Impaired performance of alpha7 nicotinic receptor knockout mice in the five-choice serial reaction time task. Psychopharmacology (Berl) 189: 211–223.1701956510.1007/s00213-006-0549-2PMC1705494 | — | — | — |
| HutterS, VilellaAJ, RozasJ (2006) Genome-wide DNA polymorphism analyses using VariScan. BMC Bioinformatics 7: 409 1696853110.1186/1471-2105-7-409PMC1574356 | — | — | — |
| JoblingMA, HurlesM.E., & Tyler-SmithC. (2004) Human Evoutionary Genetics: Origins, Peoples and Disease. New York, NY: Garland Publishing. | — | — | — |
| JonesBL, RagaTO, LiebertA, ZmarzP, BekeleE, et al (2013) Diversity of lactase persistence alleles in Ethiopia: signature of a soft selective sweep. Am J Hum Genet 93: 538–544. 10.1016/j.ajhg.2013.07.008 23993196PMC3769926 | — | — | — |
| KaufmanAS, LichtenbergerEO (2002) Assessing adolescent and adult intelligence Boston, MA: Allyn and Bacon xix, 748 p. p. | — | — | — |
| KumariV, GrayJA, ffytcheDH, MitterschiffthalerMT, DasM, et al (2003) Cognitive effects of nicotine in humans: an fMRI study. Neuroimage 19: 1002–1013. 1288082810.1016/s1053-8119(03)00110-1 | — | — | — |
| LiuX, OngRT, PillaiEN, ElzeinAM, SmallKS, et al (2013) Detecting and characterizing genomic signatures of positive selection in global populations. Am J Hum Genet 92: 866–881. 10.1016/j.ajhg.2013.04.021 23731540PMC3675259 | — | — | — |
| MarthGT, CzabarkaE, MurvaiJ, SherryST (2004) The allele frequency spectrum in genome-wide human variation data reveals signals of differential demographic history in three large world populations. Genetics 166: 351–372. 1502043010.1534/genetics.166.1.351PMC1470693 | — | — | — |
| PrellerKH, HerdenerM, SchilbachL, StampfliP, HulkaLM, et al (2014) Functional changes of the reward system underlie blunted response to social gaze in cocaine users. Proc Natl Acad Sci U S A 111: 2842–2847. 10.1073/pnas.1317090111 24449854PMC3932870 | — | — | — |
| RiceJP, HartzSM, AgrawalA, AlmasyL, BennettS, et al (2012) CHRNB3 is more strongly associated with Fagerstrom test for cigarette dependence-based nicotine dependence than cigarettes per day: phenotype definition changes genome-wide association studies results. Addiction 107: 2019–2028. 10.1111/j.1360-0443.2012.03922.x 22524403PMC3427406 | — | — | — |
| RigbiA, KanyasK, YakirA, GreenbaumL, PollakY, et al (2008) Why do young women smoke? V. Role of direct and interactive effects of nicotinic cholinergic receptor gene variation on neurocognitive function. Genes Brain Behav 7: 164–172. 1755941910.1111/j.1601-183X.2007.00329.x | — | — | — |
| SabetiPC, ReichDE, HigginsJM, LevineHZ, RichterDJ, et al (2002) Detecting recent positive selection in the human genome from haplotype structure. Nature 419: 832–837. 1239735710.1038/nature01140 | — | — | — |
| SacconeSF, HinrichsAL, SacconeNL, ChaseGA, KonvickaK, et al (2007) Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs. Hum Mol Genet 16: 36–49. 1713527810.1093/hmg/ddl438PMC2270437 | — | — | — |
| SadlerB, HallerG, AgrawalA, CulverhouseR, BucholzK, et al (2014) Variants near CHRNB3-CHRNA6 are associated with DSM-5 cocaine use disorder: evidence for pleiotropy. Sci Rep 4: 4497 10.1038/srep04497 24675634PMC4894386 | — | — | — |
| SpitzMR, AmosCI, DongQ, LinJ, WuX (2008) The CHRNA5-A3 region on chromosome 15q24-25.1 is a risk factor both for nicotine dependence and for lung cancer. J Natl Cancer Inst 100: 1552–1556. 10.1093/jnci/djn363 18957677PMC2720751 | — | — | — |
| TajimaF (1989) Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123: 585–595. 251325510.1093/genetics/123.3.585PMC1203831 | — | — | — |
| ThielCM, ZillesK, FinkGR (2005) Nicotine modulates reorienting of visuospatial attention and neural activity in human parietal cortex. Neuropsychopharmacology 30: 810–820. 1566872610.1038/sj.npp.1300633 | — | — | — |
| ThorgeirssonTE, GellerF, SulemP, RafnarT, WisteA, et al (2008) A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature 452: 638–642. 10.1038/nature06846 18385739PMC4539558 | — | — | — |
| ThorgeirssonTE, GudbjartssonDF, SurakkaI, VinkJM, AminN, et al (2010) Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. Nat Genet 42: 448–453. 10.1038/ng.573 20418888PMC3080600 | — | — | — |
| VoightBF, KudaravalliS, WenX, PritchardJK (2006) A map of recent positive selection in the human genome. PLoS Biol 4: e72 1649453110.1371/journal.pbio.0040072PMC1382018 | — | — | — |
| WangJC, CruchagaC, SacconeNL, BertelsenS, LiuP, et al (2009) Risk for nicotine dependence and lung cancer is conferred by mRNA expression levels and amino acid change in CHRNA5. Hum Mol Genet 18: 3125–3135. 10.1093/hmg/ddp231 19443489PMC2714722 | — | — | — |
| WangJC, SpiegelN, BertelsenS, LeN, McKennaN, et al (2013) Cis-regulatory variants affect CHRNA5 mRNA expression in populations of African and European ancestry. PLoS One 8: e80204 10.1371/journal.pone.0080204 24303001PMC3841173 | — | — | — |
| WeissRB, BakerTB, CannonDS, von NiederhausernA, DunnDM, et al (2008) A candidate gene approach identifies the CHRNA5-A3-B4 region as a risk factor for age-dependent nicotine addiction. PLoS Genet 4: e1000125 10.1371/journal.pgen.1000125 18618000PMC2442220 | — | — | — |
| WilliamsonSH, HubiszMJ, ClarkAG, PayseurBA, BustamanteCD, et al (2007) Localizing recent adaptive evolution in the human genome. PLoS Genet 3: e90 1754265110.1371/journal.pgen.0030090PMC1885279 | — | — | — |
| WintererG, MittelstrassK, GieglingI, LaminaC, FehrC, et al (2010) Risk gene variants for nicotine dependence in the CHRNA5-CHRNA3-CHRNB4 cluster are associated with cognitive performance. Am J Med Genet B Neuropsychiatr Genet 153B: 1448–1458. 10.1002/ajmg.b.31126 20886544 | — | — | — |
| YoungJW, MevesJM, TarantinoIS, CaldwellS, GeyerMA (2011) Delayed procedural learning in alpha7-nicotinic acetylcholine receptor knockout mice. Genes Brain Behav 10: 720–733. 10.1111/j.1601-183X.2011.00711.x 21679297PMC3918170 | — | — | — |
No papers in this knowledge base cite this source.
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Discovery of runs-of-homozygosity diplotype clusters and their associations with diseases in UK Biobank. | Naseri A et al. | — | 2024 | → |
| Combined genetic influence of the nicotinic receptor gene cluster CHRNA5/A3/B4 on nicotine dependence. | Lee SH et al. | — | 2018 | → |
| Genetic epidemiology of familial Mediterranean fever through integrative analysis of whole genome and exome sequences from Middle East and North Africa. | Koshy R et al. | — | 2018 | → |
| Pleiotropic effects of Chr15q25 nicotinic gene cluster and the relationship between smoking, cognition and ADHD. | Schuch JB et al. | — | 2016 | → |