Gisladottir Rosa S, Ivarsdottir Erna V, Helgason Agnar, Jonsson Lina, Hannesdottir Nanna K, Rutsdottir Gudrun, Arnadottir Gudny A, Skuladottir Astros, Jonsson Benedikt A, Norddahl Gudmundur L, Ulfarsson Magnus O, Helgason Hannes, Halldorsson Bjarni V, Nawaz Muhammad S, Tragante Vinicius, Sveinbjornsson Gardar, Thorgeirsson Thorgeir, Oddsson Asmundur, Kristjansson Ragnar P, Bjornsdottir Gyda, Thorgeirsson Gudmundur, Jonsdottir Ingileif, Holm Hilma, Gudbjartsson Daniel F, Thorsteinsdottir Unnur, Stefansson Hreinn, Sulem Patrick, Stefansson Kari
deCODE Genetics/Amgen Inc., Sturlugata 8, 101 Reykjavik, Iceland; School of Humanities, University of Iceland, Saemundargata 2, 102 Reykjavik, Iceland.
deCODE Genetics/Amgen Inc., Sturlugata 8, 101 Reykjavik, Iceland; School of Engineering and Natural Sciences, University of Iceland, Dunhagi 5, 107 Reykjavik, Iceland.
Curr Biol. 2020 Dec 7;30(23):4643-4653.e3. doi: 10.1016/j.cub.2020.09.012. Epub 2020 Oct 8.
Olfactory receptor (OR) genes in humans form a special class characterized by unusually high DNA sequence diversity, which should give rise to differences in perception and behavior. In the largest genome-wide association study to date based on olfactory testing, we investigated odor perception and naming with smell tasks performed by 9,122 Icelanders, with replication in a separate sample of 2,204 individuals. We discovered an association between a low-frequency missense variant in TAAR5 and reduced intensity rating of fish odor containing trimethylamine (p.Ser95Pro, p = 5.6 × 10). We demonstrate that TAAR5 genotype affects aversion to fish odor, reflected by linguistic descriptions of the odor and pleasantness ratings. We also discovered common sequence variants in two canonical olfactory receptor loci that associate with increased intensity and naming of licorice odor (trans-anethole: lead variant p.Lys233Asn in OR6C70, p = 8.8 × 10 and p = 1.4 × 10) and enhanced naming of cinnamon (trans-cinnamaldehyde; intergenic variant rs317787-T, p = 5.0 × 10). Together, our results show that TAAR5 genotype variation influences human odor responses and highlight that sequence diversity in canonical OR genes can lead to enhanced olfactory ability, in contrast to the view that greater tolerance for mutations in the human OR repertoire leads to diminished function.
人类的嗅觉受体（OR）基因构成了一个特殊的类别，其特点是DNA序列多样性异常高，这可能会导致感知和行为上的差异。在迄今为止基于嗅觉测试的最大规模全基因组关联研究中，我们通过9122名冰岛人执行的嗅觉任务来调查气味感知和命名，并在另外2204人的样本中进行了重复验证。我们发现TAAR5基因中的一个低频错义变体与含有三甲胺的鱼腥味强度评级降低之间存在关联（p.Ser95Pro，p = 5.6×10）。我们证明TAAR5基因型会影响对鱼腥味的厌恶，这在气味的语言描述和愉悦度评级中有所体现。我们还在两个典型的嗅觉受体基因座中发现了常见的序列变体，它们与甘草气味（反式茴香脑：OR6C70中的主要变体p.Lys233Asn，p = 8.8×10和p = 1.4×10）的强度增加和命名以及肉桂气味（反式肉桂醛；基因间变体rs317787 - T，p = 5.0×10）的命名增强有关。总之，我们的结果表明TAAR5基因型变异会影响人类的气味反应，并强调典型OR基因中的序列多样性可导致嗅觉能力增强，这与人类OR库中对突变的更大耐受性会导致功能减弱的观点相反。
