PLoS genetics · 2014

Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.

СтатьяМетаанализПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен

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Hoggart Clive J, Venturini Giulia, Mangino Massimo, Gomez Felicia, Ascari Giulia, Zhao Jing Hua, Teumer Alexander, Winkler Thomas W, Tšernikova Natalia, Luan Jian'an, Mihailov Evelin, Ehret Georg B, Zhang Weihua, Lamparter David, Esko Tõnu, Macé Aurelien, Rüeger Sina, Bochud Pierre-Yves, Barcella Matteo, Dauvilliers Yves, Benyamin Beben, Evans David M, Hayward Caroline, Lopez Mary F, Franke Lude, Russo Alessia, Heid Iris M, Salvi Erika, Vendantam Sailaja, Arking Dan E, Boerwinkle Eric, Chambers John C, Fiorito Giovanni, Grallert Harald, Guarrera Simonetta, Homuth Georg, Huffman Jennifer E, Porteous David, Generation Scotland Consortium, LifeLines Cohort study, GIANT Consortium, Moradpour Darius, Iranzo Alex, Hebebrand Johannes, Kemp John P, Lammers Gert J, Aubert Vincent, Heim Markus H, Martin Nicholas G, Montgomery Grant W, Peraita-Adrados Rosa, Santamaria Joan, Negro Francesco, Schmidt Carsten O, Scott Robert A, Spector Tim D, Strauch Konstantin, Völzke Henry, Wareham Nicholas J, Yuan Wei, Bell Jordana T, Chakravarti Aravinda, Kooner Jaspal S, Peters Annette, Matullo Giuseppe, Wallaschofski Henri, Whitfield John B, Paccaud Fred, Vollenweider Peter, Bergmann Sven, Beckmann Jacques S, Tafti Mehdi, Hastie Nicholas D, Cusi Daniele, Bochud Murielle, Frayling Timothy M, Metspalu Andres, Jarvelin Marjo-Riitta, Scherag André, Smith George Davey, Borecki Ingrid B, Rousson Valentin, Hirschhorn Joel N, Rivolta Carlo, Loos Ruth J F, Kutalik Zoltán

Аннотация

The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ∼4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta = 0.11 (SD), P<0.0027) compared to the respective maternal alleles. Real-time PCR experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on parental origin of the SNPs alleles (P<0.01). Our scheme opens new opportunities to exploit GWAS data of unrelated individuals to identify POEs and demonstrates that they play an important role in adult obesity.

Предметные рубрики MeSH

Adult Body Mass Index Female Gene Expression Regulation Genetic Predisposition to Disease Genome-Wide Association Study Genomic Imprinting Genotype Glucose Transport Proteins, Facilitative Humans Male Obesity Polymorphism, Single Nucleotide Potassium Channels, Tandem Pore Domain White People

Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH