Sniffing out significant “Pee values”: genome wide association study of asparagus anosmiaBMJ 2016; 355 doi: https://doi.org/10.1136/bmj.i6071 (Published 13 December 2016) Cite this as: BMJ 2016;355:i6071
- Sarah C Markt, research associate1,
- Elizabeth Nuttall, medical student1,
- Constance Turman, programmer/analyst4,
- Jennifer Sinnott, assistant professor1 5,
- Eric B Rimm, professor1 2 6,
- Ethan Ecsedy, student7,
- Robert H Unger, medical student1,
- Katja Fall, associate professor1 8 9,
- Stephen Finn, associate professor10,
- Majken K Jensen, assistant professor2 6,
- Jennifer R Rider, assistant professor1 11,
- Peter Kraft, professor1 3 4,
- Lorelei A Mucci, associate professor1 6 9
- 1Department of Epidemiology, Harvard TH Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
- 2Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
- 3Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA, USA
- 4Program in Molecular and Genetic Epidemiology, Harvard TH Chan School of Public Health, Boston MA, USA
- 5Department of Statistics, Ohio State University, Columbus, OH, USA
- 6Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
- 7Cabot School, Newton, MA, USA
- 8Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden
- 9Division of Public Health Sciences, University of Iceland, Reykjavik, Iceland
- 10Department of Pathology, Trinity College, Dublin, Republic of Ireland
- 11Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA
- Correspondence to: L A Mucci
- Accepted 1 November 2016
Objective To determine the inherited factors associated with the ability to smell asparagus metabolites in urine.
Design Genome wide association study.
Setting Nurses’ Health Study and Health Professionals Follow-up Study cohorts.
Participants 6909 men and women of European-American descent with available genetic data from genome wide association studies.
Main outcome measure Participants were characterized as asparagus smellers if they strongly agreed with the prompt “after eating asparagus, you notice a strong characteristic odor in your urine,” and anosmic if otherwise. We calculated per-allele estimates of asparagus anosmia for about nine million single nucleotide polymorphisms using logistic regression. P values <5×10-8 were considered as genome wide significant.
Results 58.0% of men (n=1449/2500) and 61.5% of women (n=2712/4409) had anosmia. 871 single nucleotide polymorphisms reached genome wide significance for asparagus anosmia, all in a region on chromosome 1 (1q44: 248139851-248595299) containing multiple genes in the olfactory receptor 2 (OR2) family. Conditional analyses revealed three independent markers associated with asparagus anosmia: rs13373863, rs71538191, and rs6689553.
Conclusion A large proportion of people have asparagus anosmia. Genetic variation near multiple olfactory receptor genes is associated with the ability of an individual to smell the metabolites of asparagus in urine. Future replication studies are necessary before considering targeted therapies to help anosmic people discover what they are missing.
Contributors: All authors conceived and designed the study, analyzed the data, and prepared the manuscript. SCM and EN contributed equally to this manuscript. PK and LAM share last authorship. LAM is guarantor.
Funding: This work was supported by funding from the National Cancer Institute at the National Institutes of Health (NIH) (UM1 CA167552, R01 HL35464, UM1 CA186107, R01 CA49449, R01 HL034594, R01 HL088521); National Cancer Institute at the NIH training grant (NIH T32 CA09001 to SCM); and the Prostate Cancer Foundation (to LAM and JRR).
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations, including asparagus growers, that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Furthermore, the authors do not avoid asparagus consumption. Some of the authors report asparagus anosmia; the non-anosmic wish to remain anonymous. However, the first and last authors admit they can both produce and detect the “filthy and disagreeable smell in the urine.”
Ethical approval: The study protocols were approved by the institutional review boards of Harvard TH Chan School of Public Health and Partners Healthcare.
Data sharing: Data from the genome wide association studies are provided on dbGAP (www.ncbi.nlm.nih.gov/gap), a database on genotypes and phenotypes.
Transparency: The lead author (LAM) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
We thank the participants of the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS) for making this study possible and colleagues in the Transdisciplinary Prostate Cancer Partnership (www.topcapteam.org) for lively discussions around asparagus anosmia. The NHS Breast Cancer genome wide association study (GWAS) was performed as part of the cancer genetic markers of susceptibility initiative of the National Cancer Institute. The NHS/HPFS type 2 diabetes GWAS is a component of a collaborative project that includes 13 other GWAS funded as part of the Gene Environment-Association Studies under the National Institutes of Health genes, environment and health initiative. A special thanks to Sonja Swanson for her intellectual and humorous input.
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