title: APOH interacts with FTO to predispose to healthy thinness.
abstract: We identified eight candidate thinness predisposition variants from the Illumina HumanExome chip genotyped on members of pedigrees selected for either healthy thinness or severe obesity. For validation, we tested the candidates for association with healthy thinness in additional pedigree members while accounting for effects of obesity-associated genes: NPFFR2, NPY2R, FTO, and MC4R. Significance was obtained for the interaction of FTO rs9939609 with APOH missense variant rs52797880 (minor allele frequency 0.054). The thinness odds ratio was estimated as 2.15 (p < 0.05) for the combination of APOH heterozygote with the homozygote for the non-obesity FTO allele. Significance was not obtained for any other combination of a candidate variant with an obesity gene or for any of the eight candidates tested independently.
authors.affiliation: Department of Human Genetics, University of Utah School of Medicine, 15 N 2030 E, Salt Lake City, UT, 84112-5330, USA. sandy@genetics.utah.edu.
authors.forename: Sandra J
authors.identifier: http://orcid.org/0000-0002-3549-5627
authors.initials: SJ
authors.lastname: Hasstedt
authors.affiliation: Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Hilary
authors.initials: H
authors.lastname: Coon
authors.affiliation: Cardiovascular Genetics Division, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Yuanpei
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Cardiovascular Genetics Division, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Ted D
authors.initials: TD
authors.lastname: Adams
authors.affiliation: Cardiovascular Genetics Division, University of Utah School of Medicine, Salt Lake City, UT, USA.|Department of Genetic Medicine, Weill Cornell Medical College, Doha, Qatar.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hunt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009765:Obesity / Q000235:genetics; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D013851:Thinness / Q000235:genetics*; D055815:Young Adult; D053482:beta 2-Glycoprotein I / Q000235:genetics* / Q000378:metabolism
chemical_list: D011506:Proteins; D053482:beta 2-Glycoprotein I; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human