TY - JOUR
T1 - Linkage of nicotine dependence and smoking behavior on 10q, 7q and 11p in twins with homogeneous genetic background
AU - Loukola, A.
AU - Broms, U.
AU - Maunu, H.
AU - Widén, E.
AU - Heikkilä, K.
AU - Siivola, M.
AU - Salo, A.
AU - Pergadia, M. L.
AU - Nyman, E.
AU - Sammalisto, S.
AU - Perola, M.
AU - Agrawal, A.
AU - Heath, A. C.
AU - Martin, N. G.
AU - Madden, P. A.F.
AU - Peltonen, L.
AU - Kaprio, J.
N1 - Funding Information:
We are grateful to the participating families for their patience and contribution. We express our appreciation to the skillful study interviewers: A Häppölä, A-M Iivonen, K Karhu, H-M Kuha, U Kulmala-Gråhn, M Mantere, K Saanakorpi, M Saarinen, R Sipilä, L Viljanen and E Voipio. We are grateful to D Statham for helping to train the interviewers. We thank P Ruokolinna for thorough data entering. We thank the excellent staff at the Finnish Genome Center: S Ekström, A Yliperttula, A Korvenpää and M Baarman for producing the genotype data, A Sarahonka and V Leppä for diligently reviewing the genotype data, A Leinonen and J Hinkula for careful data cleaning procedures and Dr J Muilu for supervising the data management team. The study is funded by the Academy of Finland Post-doctoral Fellowship to A Loukola, by Doctoral Programs of Public Health, University of Helsinki, Finland to support U Broms, by GenomEUtwin (European Union Contract No. QLG2-CT-2002-01254) to J Kaprio and L Peltonen, by NIH grant DA12854 to PAF Madden, and by Center of Excellence in Disease Genetics, Academy of Finland to L Peltonen. Data collection was supported by a NIH grant DA12854 to PAF Madden and by Academy of Finland grants to J Kaprio and M Koskenvuo. ML Pergadia is supported by NIH grant DA019951. This study forms a part of the research program of the Academy of Finland Center of Excellence in Complex Disease Genetics.
PY - 2008/6
Y1 - 2008/6
N2 - The significant worldwide health burden introduced by tobacco smoking highlights the importance of studying the genetic determinants of smoking behavior and the key factor sustaining compulsive smoking, that is, nicotine dependence (ND). We have here addressed the genetic background of smoking in a special study sample of twins, harmonized for early life events and specifically ascertained for smoking from the nationwide twin cohort of the genetically unique population of Finland. The twins and their families were carefully examined for extensive phenotype profiles and a genome-wide scan was performed to identify loci behind the smoking status, ND and the comorbid phenotype of ND and alcohol use in 505 individuals from 153 families. We replicated previous linkage findings on 10q (max logarithm of the odds (LOD) 3.12) for a smoker phenotype, and on 7q and 11p (max LOD 2.50, and 2.25, respectively) for the ND phenotype. The loci linked for ND also showed evidence for linkage for the comorbid phenotype. Our study provides confirmatory evidence for the involvement of these genome regions in the genetic etiology of smoking behavior and ND and for the first time associates drinking and smoking to a shared locus on 10q.
AB - The significant worldwide health burden introduced by tobacco smoking highlights the importance of studying the genetic determinants of smoking behavior and the key factor sustaining compulsive smoking, that is, nicotine dependence (ND). We have here addressed the genetic background of smoking in a special study sample of twins, harmonized for early life events and specifically ascertained for smoking from the nationwide twin cohort of the genetically unique population of Finland. The twins and their families were carefully examined for extensive phenotype profiles and a genome-wide scan was performed to identify loci behind the smoking status, ND and the comorbid phenotype of ND and alcohol use in 505 individuals from 153 families. We replicated previous linkage findings on 10q (max logarithm of the odds (LOD) 3.12) for a smoker phenotype, and on 7q and 11p (max LOD 2.50, and 2.25, respectively) for the ND phenotype. The loci linked for ND also showed evidence for linkage for the comorbid phenotype. Our study provides confirmatory evidence for the involvement of these genome regions in the genetic etiology of smoking behavior and ND and for the first time associates drinking and smoking to a shared locus on 10q.
UR - http://www.scopus.com/inward/record.url?scp=44049103123&partnerID=8YFLogxK
U2 - 10.1038/sj.tpj.6500464
DO - 10.1038/sj.tpj.6500464
M3 - Article
C2 - 17549066
AN - SCOPUS:44049103123
SN - 1470-269X
VL - 8
SP - 209
EP - 219
JO - Pharmacogenomics Journal
JF - Pharmacogenomics Journal
IS - 3
ER -