You could be reading the full-text of this article now if you...

If you have access to this article through your institution,
you can view this article in

Identification of CHRNA5 rare variants in African-American heavy smokers

Doyle, Glenn A.; Chou, Andrew D.; Saung, Wint Thu; Lai, Alison T.; Lohoff, Falk W.; Berrettini, Wade H.

Psychiatric Genetics:
doi: 10.1097/YPG.0000000000000029
Original Articles

Background: The common CHRNA5 mis-sense coding single-nucleotide polymorphism (SNP) rs16969968:G>A (D398N) has repeatedly been shown to confer risk for heavy smoking in individuals who carry the ‘A’ allele (encoding the 398N amino acid). The mis-sense SNP has a minor allele frequency of ∼40% in European-Americans, but only ∼7% in African-Americans ( We reasoned that there might be other mis-sense variants among African-Americans that could confer the heavy smoking phenotype (defined here as ≥20 cigarettes per day), perhaps in a manner similar to that of the D398N polymorphism in Europeans.

Materials and methods: As such, we resequenced 250 African-American heavy smokers, most of whom were homozygous ‘G’ at rs16969968:G>A (minor allele frequency of 9.6% within the population).

Results: Although many novel coding SNPs were not observed, we report an interesting, although rare (perhaps personal), variant in CHRNA5 that could result in nonsense-mediated decay of the aberrant transcript.

Conclusion: We conclude that, in African-Americans, variants (common or rare) in genes other than CHRNA5 most likely contribute toward the nicotine-dependent phenotype, either independently or in combination with variants in CHRNA5. The functional significance, on CHRNA5 expression or protein function, of the variants found here should be determined in future studies.

Author Information

Department of Psychiatry, Perelman School of Medicine, Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (

Correspondence to Glenn A. Doyle, PhD, Department of Psychiatry, Perelman School of Medicine, Center for Neurobiology and Behavior, University of Pennsylvania, Translational Research Building, Room 2231-6, 125 South 31st Street, Philadelphia, PA 19104, USA Tel: +1 215 573 4583; fax: +1 215 573 2041; e-mail:

Received June 13, 2013

Accepted November 27, 2013

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins