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Letters to the Editor   |    
Response to Kaufman and Harper Letter
Li-Shiun Chen, M.D., M.P.H., Sc.D.; Timothy B. Baker, Ph.D.; Laura J. Bierut, M.D.
Am J Psychiatry 2012;169:1118-1119. doi:10.1176/appi.ajp.2012.12060800r
View Author and Article Information

The authors’ disclosures accompany the original article.

St. Louis
Madison, Wisc.
St. Louis

Accepted July , 2012.

To the Editor: A great deal of research shows that the CHRNA5-CHRNA3-CHRNB4 haplotypes are associated with measures of smoking quantity (14). However, earlier research presented inconsistent results with regard to the association of these haplotypes with smoking cessation likelihood. Our findings show that these haplotypes can predict cessation success and also that their association with cessation likelihood differs depending on the use of smoking cessation pharmacotherapy in the quit attempt. In essence, we obtained a significant interaction effect between haplotype and treatment condition such that individuals with haplotypes that confer a heightened risk of relapse benefited much more from cessation pharmacotherapy than did individuals without such haplotypes.

In our study, we used both the Cox proportional hazards model to estimate the likelihood of smoking relapse over time and the logistic regression model to estimate the odds of smoking abstinence, and both showed greater benefit from pharmacotherapy in individuals with risk haplotypes than in those without such haplotypes. However, at one point in the article, we discussed the odds ratio generated by the logistic regression as if it reflected relative risk. In their letter, Kaufman and Harper note that the odds ratio and the relative risk ratio diverge for analyses of common events.

We agree with Kaufman and Harper’s observation and appreciate their pointing out that the results of our research appear even more striking when portrayed in terms of number needed to treat. In our study, the number needed to treat is seven when computed across all individuals regardless of their haplotype status, supporting the established effect of pharmacotherapy. However, this number varies widely depending on the individual’s haplotype. Based on their absolute risks, the number needed to treat is four for smokers with the high-risk haplotype, seven for smokers with the intermediate-risk haplotype, and >1,000 for smokers with the low-risk haplotype. We agree with Kaufman and Harper that a number needed to treat of four is an impressive finding compared with the numbers needed to treat of many existing pharmacotherapies. The wide variation between smokers with different haplotypes supports the notion that personalized smoking cessation intervention based on genotype could meaningfully increase the efficiency of such treatment.

Liu  JZ;  Tozzi  F;  Waterworth  DM;  Pillai  SG;  Muglia  P;  Middleton  L;  Berrettini  W;  Knouff  CW;  Yuan  X;  Waeber  G;  Vollenweider  P;  Preisig  M;  Wareham  NJ;  Zhao  JH;  Loos  RJ;  Barroso  I;  Khaw  KT;  Grundy  S;  Barter  P;  Mahley  R;  Kesaniemi  A;  McPherson  R;  Vincent  JB;  Strauss  J;  Kennedy  JL;  Farmer  A;  McGuffin  P;  Day  R;  Matthews  K;  Bakke  P;  Gulsvik  A;  Lucae  S;  Ising  M;  Brueckl  T;  Horstmann  S;  Wichmann  HE;  Rawal  R;  Dahmen  N;  Lamina  C;  Polasek  O;  Zgaga  L;  Huffman  J;  Campbell  S;  Kooner  J;  Chambers  JC;  Burnett  MS;  Devaney  JM;  Pichard  AD;  Kent  KM;  Satler  L;  Lindsay  JM;  Waksman  R;  Epstein  S;  Wilson  JF;  Wild  SH;  Campbell  H;  Vitart  V;  Reilly  MP;  Li  M;  Qu  L;  Wilensky  R;  Matthai  W;  Hakonarson  HH;  Rader  DJ;  Franke  A;  Wittig  M;  Schäfer  A;  Uda  M;  Terracciano  A;  Xiao  X;  Busonero  F;  Scheet  P;  Schlessinger  D;  St Clair  D;  Rujescu  D;  Abecasis  GR;  Grabe  HJ;  Teumer  A;  Völzke  H;  Petersmann  A;  John  U;  Rudan  I;  Hayward  C;  Wright  AF;  Kolcic  I;  Wright  BJ;  Thompson  JR;  Balmforth  AJ;  Hall  AS;  Samani  NJ;  Anderson  CA;  Ahmad  T;  Mathew  CG;  Parkes  M;  Satsangi  J;  Caulfield  M;  Munroe  PB;  Farrall  M;  Dominiczak  A;  Worthington  J;  Thomson  W;  Eyre  S;  Barton  A;  Mooser  V;  Francks  C;  Marchini  J;  Wellcome Trust Case Control Consortium:  Meta-analysis and imputation refines the association of 15q25 with smoking quantity.  Nat Genet 2010; 42:436–440
[PubMed]
[CrossRef]
 
Saccone  NL;  Culverhouse  RC;  Schwantes-An  TH;  Cannon  DS;  Chen  X;  Cichon  S;  Giegling  I;  Han  S;  Han  Y;  Keskitalo-Vuokko  K;  Kong  X;  Landi  MT;  Ma  JZ;  Short  SE;  Stephens  SH;  Stevens  VL;  Sun  L;  Wang  Y;  Wenzlaff  AS;  Aggen  SH;  Breslau  N;  Broderick  P;  Chatterjee  N;  Chen  J;  Heath  AC;  Heliövaara  M;  Hoft  NR;  Hunter  DJ;  Jensen  MK;  Martin  NG;  Montgomery  GW;  Niu  T;  Payne  TJ;  Peltonen  L;  Pergadia  ML;  Rice  JP;  Sherva  R;  Spitz  MR;  Sun  J;  Wang  JC;  Weiss  RB;  Wheeler  W;  Witt  SH;  Yang  BZ;  Caporaso  NE;  Ehringer  MA;  Eisen  T;  Gapstur  SM;  Gelernter  J;  Houlston  R;  Kaprio  J;  Kendler  KS;  Kraft  P;  Leppert  MF;  Li  MD;  Madden  PA;  Nöthen  MM;  Pillai  S;  Rietschel  M;  Rujescu  D;  Schwartz  A;  Amos  CI;  Bierut  LJ:  Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta-analysis and comparison with lung cancer and COPD.  PLoS Genet 2010; 6:e1001053
[PubMed]
[CrossRef]
 
Tobacco and Genetics Consortium:  Genome-wide meta-analyses identify multiple loci associated with smoking behavior.  Nat Genet 2010; 42:441–447
[PubMed]
[CrossRef]
 
Thorgeirsson  TE;  Gudbjartsson  DF;  Surakka  I;  Vink  JM;  Amin  N;  Geller  F;  Sulem  P;  Rafnar  T;  Esko  T;  Walter  S;  Gieger  C;  Rawal  R;  Mangino  M;  Prokopenko  I;  Mägi  R;  Keskitalo  K;  Gudjonsdottir  IH;  Gretarsdottir  S;  Stefansson  H;  Thompson  JR;  Aulchenko  YS;  Nelis  M;  Aben  KK;  den Heijer  M;  Dirksen  A;  Ashraf  H;  Soranzo  N;  Valdes  AM;  Steves  C;  Uitterlinden  AG;  Hofman  A;  Tönjes  A;  Kovacs  P;  Hottenga  JJ;  Willemsen  G;  Vogelzangs  N;  Döring  A;  Dahmen  N;  Nitz  B;  Pergadia  ML;  Saez  B;  De Diego  V;  Lezcano  V;  Garcia-Prats  MD;  Ripatti  S;  Perola  M;  Kettunen  J;  Hartikainen  AL;  Pouta  A;  Laitinen  J;  Isohanni  M;  Huei-Yi  S;  Allen  M;  Krestyaninova  M;  Hall  AS;  Jones  GT;  van Rij  AM;  Mueller  T;  Dieplinger  B;  Haltmayer  M;  Jonsson  S;  Matthiasson  SE;  Oskarsson  H;  Tyrfingsson  T;  Kiemeney  LA;  Mayordomo  JI;  Lindholt  JS;  Pedersen  JH;  Franklin  WA;  Wolf  H;  Montgomery  GW;  Heath  AC;  Martin  NG;  Madden  PA;  Giegling  I;  Rujescu  D;  Järvelin  MR;  Salomaa  V;  Stumvoll  M;  Spector  TD;  Wichmann  HE;  Metspalu  A;  Samani  NJ;  Penninx  BW;  Oostra  BA;  Boomsma  DI;  Tiemeier  H;  van Duijn  CM;  Kaprio  J;  Gulcher  JR;  McCarthy  MI;  Peltonen  L;  Thorsteinsdottir  U;  Stefansson  K;  ENGAGE Consortium:  Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior.  Nat Genet 2010; 42:448–453
[PubMed]
[CrossRef]
 
References Container
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References

Liu  JZ;  Tozzi  F;  Waterworth  DM;  Pillai  SG;  Muglia  P;  Middleton  L;  Berrettini  W;  Knouff  CW;  Yuan  X;  Waeber  G;  Vollenweider  P;  Preisig  M;  Wareham  NJ;  Zhao  JH;  Loos  RJ;  Barroso  I;  Khaw  KT;  Grundy  S;  Barter  P;  Mahley  R;  Kesaniemi  A;  McPherson  R;  Vincent  JB;  Strauss  J;  Kennedy  JL;  Farmer  A;  McGuffin  P;  Day  R;  Matthews  K;  Bakke  P;  Gulsvik  A;  Lucae  S;  Ising  M;  Brueckl  T;  Horstmann  S;  Wichmann  HE;  Rawal  R;  Dahmen  N;  Lamina  C;  Polasek  O;  Zgaga  L;  Huffman  J;  Campbell  S;  Kooner  J;  Chambers  JC;  Burnett  MS;  Devaney  JM;  Pichard  AD;  Kent  KM;  Satler  L;  Lindsay  JM;  Waksman  R;  Epstein  S;  Wilson  JF;  Wild  SH;  Campbell  H;  Vitart  V;  Reilly  MP;  Li  M;  Qu  L;  Wilensky  R;  Matthai  W;  Hakonarson  HH;  Rader  DJ;  Franke  A;  Wittig  M;  Schäfer  A;  Uda  M;  Terracciano  A;  Xiao  X;  Busonero  F;  Scheet  P;  Schlessinger  D;  St Clair  D;  Rujescu  D;  Abecasis  GR;  Grabe  HJ;  Teumer  A;  Völzke  H;  Petersmann  A;  John  U;  Rudan  I;  Hayward  C;  Wright  AF;  Kolcic  I;  Wright  BJ;  Thompson  JR;  Balmforth  AJ;  Hall  AS;  Samani  NJ;  Anderson  CA;  Ahmad  T;  Mathew  CG;  Parkes  M;  Satsangi  J;  Caulfield  M;  Munroe  PB;  Farrall  M;  Dominiczak  A;  Worthington  J;  Thomson  W;  Eyre  S;  Barton  A;  Mooser  V;  Francks  C;  Marchini  J;  Wellcome Trust Case Control Consortium:  Meta-analysis and imputation refines the association of 15q25 with smoking quantity.  Nat Genet 2010; 42:436–440
[PubMed]
[CrossRef]
 
Saccone  NL;  Culverhouse  RC;  Schwantes-An  TH;  Cannon  DS;  Chen  X;  Cichon  S;  Giegling  I;  Han  S;  Han  Y;  Keskitalo-Vuokko  K;  Kong  X;  Landi  MT;  Ma  JZ;  Short  SE;  Stephens  SH;  Stevens  VL;  Sun  L;  Wang  Y;  Wenzlaff  AS;  Aggen  SH;  Breslau  N;  Broderick  P;  Chatterjee  N;  Chen  J;  Heath  AC;  Heliövaara  M;  Hoft  NR;  Hunter  DJ;  Jensen  MK;  Martin  NG;  Montgomery  GW;  Niu  T;  Payne  TJ;  Peltonen  L;  Pergadia  ML;  Rice  JP;  Sherva  R;  Spitz  MR;  Sun  J;  Wang  JC;  Weiss  RB;  Wheeler  W;  Witt  SH;  Yang  BZ;  Caporaso  NE;  Ehringer  MA;  Eisen  T;  Gapstur  SM;  Gelernter  J;  Houlston  R;  Kaprio  J;  Kendler  KS;  Kraft  P;  Leppert  MF;  Li  MD;  Madden  PA;  Nöthen  MM;  Pillai  S;  Rietschel  M;  Rujescu  D;  Schwartz  A;  Amos  CI;  Bierut  LJ:  Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta-analysis and comparison with lung cancer and COPD.  PLoS Genet 2010; 6:e1001053
[PubMed]
[CrossRef]
 
Tobacco and Genetics Consortium:  Genome-wide meta-analyses identify multiple loci associated with smoking behavior.  Nat Genet 2010; 42:441–447
[PubMed]
[CrossRef]
 
Thorgeirsson  TE;  Gudbjartsson  DF;  Surakka  I;  Vink  JM;  Amin  N;  Geller  F;  Sulem  P;  Rafnar  T;  Esko  T;  Walter  S;  Gieger  C;  Rawal  R;  Mangino  M;  Prokopenko  I;  Mägi  R;  Keskitalo  K;  Gudjonsdottir  IH;  Gretarsdottir  S;  Stefansson  H;  Thompson  JR;  Aulchenko  YS;  Nelis  M;  Aben  KK;  den Heijer  M;  Dirksen  A;  Ashraf  H;  Soranzo  N;  Valdes  AM;  Steves  C;  Uitterlinden  AG;  Hofman  A;  Tönjes  A;  Kovacs  P;  Hottenga  JJ;  Willemsen  G;  Vogelzangs  N;  Döring  A;  Dahmen  N;  Nitz  B;  Pergadia  ML;  Saez  B;  De Diego  V;  Lezcano  V;  Garcia-Prats  MD;  Ripatti  S;  Perola  M;  Kettunen  J;  Hartikainen  AL;  Pouta  A;  Laitinen  J;  Isohanni  M;  Huei-Yi  S;  Allen  M;  Krestyaninova  M;  Hall  AS;  Jones  GT;  van Rij  AM;  Mueller  T;  Dieplinger  B;  Haltmayer  M;  Jonsson  S;  Matthiasson  SE;  Oskarsson  H;  Tyrfingsson  T;  Kiemeney  LA;  Mayordomo  JI;  Lindholt  JS;  Pedersen  JH;  Franklin  WA;  Wolf  H;  Montgomery  GW;  Heath  AC;  Martin  NG;  Madden  PA;  Giegling  I;  Rujescu  D;  Järvelin  MR;  Salomaa  V;  Stumvoll  M;  Spector  TD;  Wichmann  HE;  Metspalu  A;  Samani  NJ;  Penninx  BW;  Oostra  BA;  Boomsma  DI;  Tiemeier  H;  van Duijn  CM;  Kaprio  J;  Gulcher  JR;  McCarthy  MI;  Peltonen  L;  Thorsteinsdottir  U;  Stefansson  K;  ENGAGE Consortium:  Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior.  Nat Genet 2010; 42:448–453
[PubMed]
[CrossRef]
 
References Container
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