Agrawal, Arpana

Goate, A

Heath, A C

Kaprio, J

Madden, P A.F.

Martin, N G

Montgomery, G W

Pergadia, M L

Rice, J P

Saccone, S F

Todd, R D

Wang, J C

Digital Commons@Becker

Washington University School of MedicineDigital Commons@BeckerPosters 2007: Alcohol Use Across the Lifespan2007Genome-wide linkage analysis for quantitativeindices of alcohol consumption in Australian adults.Results from the Nicotine Addiction GeneticsProjectArpana AgrawalA C. HeathS F. SacconeM L. PergadiaJ C. WangSee next page for additional authorsFollow this and additional works at: http://digitalcommons.wustl.edu/guzeposter2007Part of the Medicine and Health Sciences CommonsThis Poster is brought to you for free and open access by the 2007: Alcohol Use Across the Lifespan at Digital Commons@Becker. It has been acceptedfor inclusion in Posters by an authorized administrator of Digital Commons@Becker. For more information, please contact engeszer@wustl.edu.Recommended CitationAgrawal, Arpana; Heath, A C.; Saccone, S F.; Pergadia, M L.; Wang, J C.; Montgomery, G W.; Goate, A; Rice, J P.; Kaprio, J; Todd, RD.; Martin, N G.; and Madden, P A.F., "Genome-wide linkage analysis for quantitative indices of alcohol consumption in Australianadults. Results from the Nicotine Addiction Genetics Project" (2007). Posters. Paper 18 Samuel B. Guze Symposium on Alcoholism.http://digitalcommons.wustl.edu/guzeposter2007/18AuthorsArpana Agrawal, A C. Heath, S F. Saccone, M L. Pergadia, J C. Wang, G W. Montgomery, A Goate, J P. Rice, JKaprio, R D. Todd, N G. Martin, and P A.F. MaddenThis poster is available at Digital Commons@Becker: http://digitalcommons.wustl.edu/guzeposter2007/18Genome-wide Linkage Analysis forQuantitative Indices of  Alcohol Consumption in Australian Adults Results from the Nicotine Addiction Genetics ProjectArpana Agrawal; A. C. Heath; S.F. Saccone; M.L. Pergadia; J.C. Wang; G. W. Montgomery; A. Goate; J. P. Rice; J. Kaprio; R.D. Todd; N.G. Martin; P.A. F. Madden.Pamela Madden, Ph.D.John Rice, Ph.D.Alison Goate, D.Phil.Andrew Heath, D.Phil.Richard Todd, Ph.D., M.D.Alexandre Todorov, Ph.D.Washington University School of  Medicine, USANicholas Martin, Ph.D.Queensland Institute of  Medical Research, AustraliaJaakko Kaprio, M.D., Ph.D.Leena Peltonen, M.D., Ph.D.Markku Koskenvuo, M.D., Ph.D.University of  Helsinki, FinlandNICOTINE GENETICS CONSORTIUM      SENIOR INVESTIGATORSALCOHOL DEPENDENCE• Heritability in adult samples is 40-60%;• Linkage analyses in dense multiplex families show linkage on chromosomes 1, 2, 4, 6, 7, 9, 11;• Strength: Diagnostic, Clinical Relevance, Comparability across studies;• Limitations: Psychometric weakness, underpowered in samples ascertained for other traits;Quantitative Indices of  Alcohol Consumption• Maximum alcohol consumption in 24-hours (MaxDrinks)• Frequency of  alcohol consumption during heaviest 12-month period• Weekly consumption during heaviest 12-month period• Frequency of  drinking to intoxication during heaviest 12-month period• Maximum drinks consumed till toleranceAlcoholism and Alcohol Consumption: Genetic overlapTable 1. Twin-cotwin correlations between quantitative indices of alcohol consumption and DSM-IV alcohol dependence in 6,257 adult Australian twins. MZ pairs shown in lower diagonal, DZ pairs in upper diagonalAlcoholism Maxdrink Freq Quant/dayDrinks toIntoxicationMax ToleranceAlcoholism 0.39 | 0.15 0.12 0.14 0.16 0.13 0.15Maxdrinks0.35 0.63 | 0.24 0.2 0.22 0.21 0.17Frequency 0.28 0.44 0.50 | 0.23 0.14 0.19 0.14Quantity/day 0.29 0.48 0.27 0.42 | 0.24 0.18 0.17Drinks to Intoxication0.35 0.41 0.39 0.32 0.45 | 0.19 0.11Max Tolerance 0.22 0.48 0.34 0.37 0.39 0.39 | 0.15MZ BELOW DIAGONAL; DZ ABOVE DIAGONAL;AIMTo conduct linkage analyses for 6quantitative indices of alcoholconsumption in the Australian componentof the NICOTINE ADDICTION GENETICSPROJECT (PI Madden).METHODS• Variables were normalized by adjusting for skewness and kurtosis;• PROC FACTOR was used to create a factor score on the normalized variables;• All variables, except the factor score were log-transformed, to approximate a normal distribution;• PROC REG was used to eliminate confounding effects of gender and age;• Residuals from the BIGSIB community sample were used to score residuals from NAG• MERLIN-REGRESS was used for singlepoint and multipoint linkage analyses, with means and variances from BIGSIB, and h2=0.50;Australian NAG SampleAustralian families with at least one currentor former heavy smoker (defined as smokingat least a pack a day or 40 or morecigarettes in their lifetime) (65) wereidentified from Twin89, Twin81 andSpouse81. The heavy smoking member of adiscordant twin pair or a randomly selectedmember from a concordant heavy smokingtwin pair or a spouse, either a heavy smokerthemselves or married to a heavy smokingtwin, were invited to participate.00.511.522.533.51 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22ChromosomeSinglepoint LOD scoreFactor ScoreMaxdrinksIntoxicationFrequencyQuantityToleranceFigure 3. Singlepoint LOD scores for quantitative indices of alcohol consumption in Australian adults* Regions with putative candidate genes for alcohol-related traits**CANDIDATE GENES ON CHROMOSOME 7pNeuropeptide YAssociation with ethanol uptake in murine modelsNeuropeptide Y A 36-amino acid neurotransmitter found in the brain and autonomic nervous system; The receptor protein that NPY operates on is a G-protein coupled receptor in the rhodopsin like GPCR family; Demonstrated role in animal models for feeding behavior and ethanol consumption; The Leu7Pro polymorphism in NPY is associated with increased alcohol consumption in humans (Lappalainen et al., 2006)Cholinergic Muscarinic Receptor 2 Muscarinic receptors membrane-bound acetylcholine receptors that are more sensitive to muscarine than to nicotine; G-protein coupled, causing decrease in cAMP in the cell, leading to inhibitory-type effects.  CHRM2 receptors are found in cardiac tissue and cause a slowing of  sinoatrial depolarization and a decrease in conduction velocity; CHRM2 is associated with alcohol and drug dependence, with depressive disorders and IQ;CANDIDATE GENES ON CHROMOSOME 7qCholinergic receptor, muscarinic 2Association with alcohol and illicit drug dependenceSAMPLEDNA and diagnostic interview data wereavailable on 2,185 individuals from 508nuclear families, which includes 658founders (parents, with 250 families withboth parents genotyped) and 1527 offspring(mean age 40 years), including sibling pairs.

Genome-wide linkage analysis for quantitative indices of alcohol consumption in Australian adults. Results from the Nicotine Addiction Genetics Project

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Genome-wide linkage analysis for quantitative indices of alcohol consumption in Australian adults. Results from the Nicotine Addiction Genetics Project

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