Sniffing out significant "Pee values": genome wide association study of asparagus anosmia

doi:10.1136/bmj.i6071

. 2016 Dec 13:355:i6071.

doi: 10.1136/bmj.i6071.

Sniffing out significant "Pee values": genome wide association study of asparagus anosmia

Sarah C Markt¹, Elizabeth Nuttall¹, Constance Turman², Jennifer Sinnott^{1

3}, Eric B Rimm^{1

4

5}, Ethan Ecsedy⁶, Robert H Unger¹, Katja Fall^{1

7

8}, Stephen Finn⁹, Majken K Jensen^{4

5}, Jennifer R Rider^{1

10}, Peter Kraft^{1

11

2}, Lorelei A Mucci^{12

5

8}

Affiliations

¹ Department of Epidemiology, Harvard TH Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.
² Program in Molecular and Genetic Epidemiology, Harvard TH Chan School of Public Health, Boston MA, USA.
³ Department of Statistics, Ohio State University, Columbus, OH, USA.
⁴ Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.
⁵ Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Cabot School, Newton, MA, USA.
⁷ Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden.
⁸ Division of Public Health Sciences, University of Iceland, Reykjavik, Iceland.
⁹ Department of Pathology, Trinity College, Dublin, Republic of Ireland.
¹⁰ Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
¹¹ Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA, USA.
¹² Department of Epidemiology, Harvard TH Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA lmucci@hsph.harvard.edu.

PMID: 27965198
PMCID: PMC5154975
DOI: 10.1136/bmj.i6071

Sniffing out significant "Pee values": genome wide association study of asparagus anosmia

Sarah C Markt et al. BMJ. 2016.

. 2016 Dec 13:355:i6071.

doi: 10.1136/bmj.i6071.

Authors

Affiliations

¹ Department of Epidemiology, Harvard TH Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.
² Program in Molecular and Genetic Epidemiology, Harvard TH Chan School of Public Health, Boston MA, USA.
³ Department of Statistics, Ohio State University, Columbus, OH, USA.
⁴ Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.
⁵ Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Cabot School, Newton, MA, USA.
⁷ Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden.
⁸ Division of Public Health Sciences, University of Iceland, Reykjavik, Iceland.
⁹ Department of Pathology, Trinity College, Dublin, Republic of Ireland.
¹⁰ Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
¹¹ Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA, USA.
¹² Department of Epidemiology, Harvard TH Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA lmucci@hsph.harvard.edu.

PMID: 27965198
PMCID: PMC5154975
DOI: 10.1136/bmj.i6071

Abstract

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.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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Conflict of interest statement

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.”

Figures

None — **Fig 1** Manhattan plot showing results of genome wide association studies for asparagus anosmia. Chr=chromosome

See this image and copyright information in PMC

Comment in

Authors' reply to Rishniw.
Markt SC, Mucci LA. Markt SC, et al. BMJ. 2017 Jun 16;357:j2910. doi: 10.1136/bmj.j2910. BMJ. 2017. PMID: 28623236 No abstract available.
"Perception v production" of asparagus odour in urine needs to be determined in a controlled study.
Rishniw M. Rishniw M. BMJ. 2017 Jun 16;357:j2882. doi: 10.1136/bmj.j2882. BMJ. 2017. PMID: 28623245 No abstract available.

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References

1. Lémery L. A treatise of all sorts of foods: both animal and vegetable: also of drinkables: giving an account how to chuse the best sort of all kinds; of the good and bad effects they produce; the principles they abound with; the time, age, and constitution they are adapted to. Wherin their nature and use is explain’d according to the sentiments of the most eminent physicians and naturalists, antient and modern. T Osborne, 1745.
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1. White RH. Occurrence of S-methyl thioesters in urines of humans after they have eaten asparagus. Science 1975;189:810-1. 10.1126/science.1162354 pmid:1162354. - DOI - PubMed

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[1] Lémery L. A treatise of all sorts of foods: both animal and vegetable: also of drinkables: giving an account how to chuse the best sort of all kinds; of the good and bad effects they produce; the principles they abound with; the time, age, and constitution they are adapted to. Wherin their nature and use is explain’d according to the sentiments of the most eminent physicians and naturalists, antient and modern. T Osborne, 1745.

[2] Lémery L. A treatise of all sorts of foods: both animal and vegetable: also of drinkables: giving an account how to chuse the best sort of all kinds; of the good and bad effects they produce; the principles they abound with; the time, age, and constitution they are adapted to. Wherin their nature and use is explain’d according to the sentiments of the most eminent physicians and naturalists, antient and modern. T Osborne, 1745.

[3] Franklin B. Letter to the Royal Academy of Brussels, c. 1781.

[4] Franklin B. Letter to the Royal Academy of Brussels, c. 1781.

[5] Franklin B.Fart Proudly: Writings of Benjamin Franklin You Never Read in School. North Atlantic Books, 2003.

[6] Franklin B.Fart Proudly: Writings of Benjamin Franklin You Never Read in School. North Atlantic Books, 2003.

[7] Proust M. Swann’s Way.Henry Holt, 1922.

[8] Proust M. Swann’s Way.Henry Holt, 1922.

[9] White RH. Occurrence of S-methyl thioesters in urines of humans after they have eaten asparagus. Science 1975;189:810-1. 10.1126/science.1162354 pmid:1162354. - DOI - PubMed

[10] White RH. Occurrence of S-methyl thioesters in urines of humans after they have eaten asparagus. Science 1975;189:810-1. 10.1126/science.1162354 pmid:1162354. - DOI - PubMed

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Sniffing out significant "Pee values": genome wide association study of asparagus anosmia

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Sniffing out significant "Pee values": genome wide association study of asparagus anosmia

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