title: Genetic taste blindness to bitter and body composition in childhood: a Mendelian randomization design.
abstract: BACKGROUND
  The ability to taste 6-n-propylthiouracil (PROP) may be associated with body composition, but previous findings from observational studies are conflicting and cannot be interpreted causally. The aim of this study was to estimate the causal association between PROP taster status and body composition in a population-based cohort study.
  
  
  METHODS
  The study was embedded in a population-based prospective birth cohort study. The TAS2R38 genotype (rs713598) was used as an instrumental variable (IV) to obtain unbiased effect estimates of the relation between PROP taster status and body weight (n=3778). Adiposity measures included body mass index (BMI) and fat mass measured by dual- energy X-ray absorptiometry scan at the child's age of 6 years. Associations were investigated using both ordinary linear regression (OLS) and two-stage least squares regression (2SLS).
  
  
  RESULTS
  Non-taster girls had higher BMI standard deviation scores (SDS) and higher body fat as compared with taster girls (results from linear regression BMI SDS: -0.09, P=0.023, body fat mass (%): -0.49, P=0.028). The TAS2R38 genotype predicted PROP phenotype (F=240), indicating a strong IV. The 2SLS effect estimates were imprecise but similar to the observational estimates (-0.08 for BMI SDS and -0.46 for body fat mass %) and were not significantly different from the OLS results (Hausman test: P>0.10). For boys there were no differences observed between tasters and non-tasters.
  
  
  CONCLUSIONS
  Our findings suggest a causal relation between PROP taster status and body weight among 6-year-old girls; Mendelian randomization was consistent with conventional estimates. In contrast, body weight among boys appeared to be independent of the PROP taster status. Further research should focus on possible underlying pathways, such as dietary behavior.
authors.affiliation: 1] The Generation R Study Group, Erasmus Medical Centre, Rotterdam, The Netherlands [2] Department of Public Health, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: S H
authors.initials: SH
authors.lastname: Bouthoorn
authors.affiliation: Department of Public Health, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: F J
authors.initials: FJ
authors.lastname: van Lenthe
authors.affiliation: 1] The Generation R Study Group, Erasmus Medical Centre, Rotterdam, The Netherlands [2] Department of Pediatrics, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: Kiefte-de Jong
authors.affiliation: 1] The Generation R Study Group, Erasmus Medical Centre, Rotterdam, The Netherlands [2] Department of Pediatrics, Erasmus Medical Centre, Rotterdam, The Netherlands [3] Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: H R
authors.initials: HR
authors.lastname: Taal
authors.affiliation: 1] The Generation R Study Group, Erasmus Medical Centre, Rotterdam, The Netherlands [2] Department of Public Health, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: A I
authors.initials: AI
authors.lastname: Wijtzes
authors.affiliation: 1] The Generation R Study Group, Erasmus Medical Centre, Rotterdam, The Netherlands [2] Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Hofman
authors.affiliation: 1] The Generation R Study Group, Erasmus Medical Centre, Rotterdam, The Netherlands [2] Department of Pediatrics, Erasmus Medical Centre, Rotterdam, The Netherlands [3] Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: V W V
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Glymour
authors.affiliation: Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Rivadeneira
authors.affiliation: Department of Public Health, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Raat
mesh_terms: D015502:Absorptiometry, Photon; D000370:Ageusia / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D001823:Body Composition; D002648:Child; D015331:Cohort Studies; D004032:Diet; D005247:Feeding Behavior; D005260:Female; D005518:Food Preferences; D005838:Genotype; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis; D011441:Propylthiouracil; D011446:Prospective Studies; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D011795:Surveys and Questionnaires; D013649:Taste / Q000235:genetics; D000098706:Taste Receptors, Type 2
chemical_list: D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; D011441:Propylthiouracil
references.citation: Int J Epidemiol. 2004 Feb;33(1):30-42
references.pmid: 15075143
references.citation: Physiol Behav. 2011 Oct 24;104(5):1065-71
references.pmid: 21712049
references.citation: Eur J Epidemiol. 2010 Nov;25(11):823-41
references.pmid: 20967563
references.citation: Proc Natl Acad Sci U S A. 1932 Jan;18(1):115-20
references.pmid: 16577421
references.citation: Physiol Behav. 2012 Nov 5;107(4):527-32
references.pmid: 22521912
references.citation: Physiol Behav. 2012 Nov 5;107(4):516-26
references.pmid: 22728784
references.citation: Chem Senses. 1995 Oct;20(5):529-33
references.pmid: 8564427
references.citation: J Am Diet Assoc. 2007 Aug;107(8):1340-8
references.pmid: 17659901
references.citation: Physiol Behav. 1994 Dec;56(6):1165-71
references.pmid: 7878086
references.citation: Cell. 2000 Mar 17;100(6):693-702
references.pmid: 10761934
references.citation: Arch Dis Child. 2012 Dec;97(12):1048-52
references.pmid: 22995095
references.citation: Eur J Epidemiol. 2007;22(12):917-23
references.pmid: 18095172
references.citation: Physiol Behav. 2002 Mar;75(3):305-12
references.pmid: 11897256
references.citation: Appetite. 2002 Feb;38(1):3-12
references.pmid: 11883912
references.citation: PLoS Med. 2008 Aug 26;5(8):e177
references.pmid: 18752343
references.citation: Science. 2003 Feb 21;299(5610):1221-5
references.pmid: 12595690
references.citation: Am J Clin Nutr. 2005 May;81(5):1005-11
references.pmid: 15883422
references.citation: J Indian Med Assoc. 2009 Jun;107(6):403-5
references.pmid: 19886379
references.citation: Obes Res. 2005 Jun;13(6):1017-23
references.pmid: 15976144
references.citation: Pediatrics. 2005 Feb;115(2):e216-22
references.pmid: 15687429
references.citation: Br J Nutr. 2013 Jan 14;109(1):137-47
references.pmid: 22475342
references.citation: Appetite. 2010 Feb;54(1):93-9
references.pmid: 19782709
references.citation: Obesity (Silver Spring). 2008 Jul;16(7):1522-8
references.pmid: 18421272
references.citation: Am J Hum Genet. 1998 Nov;63(5):1271-6
references.pmid: 9792854
references.citation: Am J Epidemiol. 2007 Sep 1;166(5):576-81
references.pmid: 17596267
references.citation: Curr Biol. 2005 Feb 22;15(4):322-7
references.pmid: 15723792
references.citation: Eur J Clin Nutr. 2000 Jan;54(1):73-80
references.pmid: 10696149
references.citation: Am J Clin Nutr. 2006 Jul;84(1):245-51
references.pmid: 16825702
references.citation: Public Health Nutr. 2010 Oct;13(10):1587-92
references.pmid: 20025833
references.citation: Appetite. 2012 Jun;58(3):991-6
references.pmid: 22381513
references.citation: Physiol Behav. 1997 Jun;61(6):949-54
references.pmid: 9177570
references.citation: Am J Epidemiol. 2012 Feb 15;175(4):332-9
references.pmid: 22247045
references.citation: Chem Senses. 2001 Jun;26(5):483-9
references.pmid: 11418493
references.citation: Am J Clin Nutr. 2010 Sep;92(3):539-45
references.pmid: 20631203
references.citation: Stat Med. 2008 Apr 15;27(8):1133-63
references.pmid: 17886233
references.citation: Obesity (Silver Spring). 2008 Oct;16(10):2289-95
references.pmid: 18719631
references.citation: Obesity (Silver Spring). 2010 Jun;18(6):1194-200
references.pmid: 19779476
references.citation: Eur J Epidemiol. 2008;23(12):801-11
references.pmid: 19101808
references.citation: Nature. 2007 Oct 18;449(7164):851-61
references.pmid: 17943122
references.citation: Obes Res. 2004 Jun;12(6):904-12
references.pmid: 15229328
references.citation: Appetite. 2004 Aug;43(1):5-9
references.pmid: 15262011
references.citation: Proc Nutr Soc. 2011 Feb;70(1):135-43
references.pmid: 21092367