Associations Between Genetic Ancestries and Nicotine Metabolism Biomarkers in the Multiethnic Cohort Study

Am J Epidemiol. 2015 Dec 1;182(11):945-51. doi: 10.1093/aje/kwv138. Epub 2015 Nov 14.


Differences in internal dose of nicotine and tobacco-derived carcinogens among ethnic/racial groups have been observed. In this study, we explicitly examined the relationships between genetic ancestries (genome-wide average) and 19 tobacco-derived biomarkers in smokers from 3 admixed groups in the Multiethnic Cohort Study (1993-present), namely, African ancestry in African Americans (n = 362), Amerindian ancestry in Latinos (n = 437), and Asian and Native Hawaiian ancestries in Native Hawaiians (n = 300). After multiple comparison adjustment, both African and Asian ancestries were significantly related to a greater level of free cotinine; African ancestry was also significantly related to lower cotinine glucuronidation (P's < 0.00156). The predicted decrease in cotinine glucuronidation was 8.6% (P = 4.5 × 10(-6)) per a 20% increase in African ancestry. Follow-up admixture mapping revealed that African ancestry in a 12-Mb region on chromosome 4q was related to lower cotinine glucuronidation (P's < 2.7 × 10(-7), smallest P = 1.5 × 10(-9)), although this is the same region reported in our previous genome-wide association study. Our results implicate a genetic ancestral component in the observed ethnic/racial variation in nicotine metabolism. Further studies are needed to identify the underlying genetic variation that could potentially be ethnic/racial specific.

Keywords: Hispanics; Pacific Islanders; association study; blacks; health disparity; nicotine addiction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Asian People / genetics
  • Biomarkers / blood
  • Black or African American / genetics
  • Cohort Studies
  • Cotinine / blood
  • Female
  • Humans
  • Indians, North American / genetics
  • Male
  • Middle Aged
  • Native Hawaiian or Other Pacific Islander / genetics
  • Nicotine / metabolism*
  • Nitrosamines / blood
  • Racial Groups / genetics*
  • Smoking / blood
  • White People / genetics


  • Biomarkers
  • Nitrosamines
  • Nicotine
  • 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
  • Cotinine