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Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index
- Source :
- Hoggart, C J, Venturini, G, Mangino, M, Gomez, F, Ascari, G, Zhao, J H, Teumer, A, Winkler, T W, Tšernikova, N, Luan, J, Mihailov, E, Ehret, G B, Zhang, W, Lamparter, D, Esko, T, Macé, A, Rüeger, S, Bochud, P-Y, Barcella, M, Dauvilliers, Y, Benyamin, B, Evans, D M, Hayward, C, Lopez, M F, Franke, L, Russo, A, Heid, I M, Salvi, E, Vendantam, S, Arking, D E, Boerwinkle, E, Chambers, J C, Fiorito, G, Grallert, H, Guarrera, S, Homuth, G, Huffman, J E, Porteous, D, Moradpour, D, Iranzo, A, Hebebrand, J, Kemp, J P, Lammers, G J, Aubert, V, Heim, M H, Martin, N G, Montgomery, G W, Peraita-Adrados, R & Santamaria, J & Hastie, N D 2014, ' Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index ', PLoS Genetics, vol. 10, no. 7, e1004508 . https://doi.org/10.1371/journal.pgen.1004508, PLoS Genetics, PLoS genetics, 10(7):1004508. PUBLIC LIBRARY SCIENCE, PLoS Genetics, 10(7):e1004508. Public Library of Science, PLoS genetics, PLoS Genetics, vol. 10, no. 7, pp. e1004508, Hoggart, C J, Venturini, G, Mangino, M, Gomez, F, Ascari, G, Hottenga, J J, Willemsen, G, Boomsma, D I, Penninx, B W J H, Uitterlinden, A G, van Duijn, C M, Visscher, P M, Rousson, V, Hirschhorn, J N, Rivolta, C, Loos, R J F & Kutali, Z 2014, ' Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index ', PLoS Genetics, vol. 10, no. 7, e1004508 . https://doi.org/10.1371/journal.pgen.1004508, PLoS Genetics, Vol 10, Iss 7, p e1004508 (2014), PLoS genetics, 10(7). Public Library of Science, Plos Genetics, 10, 7, pp. e1004508, PLoS Genet. 10, 1-12:e1004508 (2014), PLOS GENETICS, Plos Genetics, 10, e1004508, PLOS Genetics, Vol. 10, No 7 (2014) P. e1004508
- Publication Year :
- 2014
-
Abstract
- 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<br />Author Summary Large genetic association studies have revealed many genetic factors influencing common traits, such as body mass index (BMI). These studies assume that the effect of genetic variants is the same regardless of whether they are inherited from the mother or the father. In our study, we have developed a new approach that allows us to investigate variants whose impact depends on their parental origin (parent-of-origin effects), in unrelated samples when the parental origin cannot be inferred. This is feasible because at genetic markers at which such effects occur there is increased variability of the trait among individuals who inherited different genetic codes from their mother and their father compared to individuals who inherited the same genetic code from both parents. We applied this methodology to discover genetic markers with parent-of-origin effects (POEs) on BMI. This resulted in six candidate markers showing strong POE association. We then attempted to replicate the POE effects of these markers in family studies (where one can infer the parental origin of the inherited variants). Two of our candidates showed significant association in the family studies, the paternal and maternal effects of these markers were in the opposite direction.
- Subjects :
- Epigenomics
Male
Netherlands Twin Register (NTR)
body mass index
gene
SNP
Cancer Research
BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA
Potassium Channels
Glucose Transport Proteins, Facilitative
Medizin
Genome-wide association study
CHILDREN
ddc:616.07
FAMILIES
Body Mass Index
0302 clinical medicine
Polymorphism (computer science)
Genotype
LifeLines Cohort study
GENETICS & HEREDITY
Tandem Pore Domain
Genetics (clinical)
ASSOCIATIONS
ddc:616
Genetics
0303 health sciences
QUANTITATIVE TRAIT LOCI
Ecology
Genomics
Single Nucleotide
Generation Scotland Consortium
Urological cancers Radboud Institute for Health Sciences [Radboudumc 15]
OBESITY
Physical Sciences
KCNK9 protein
Epigenetics
Female
ALCOHOLISM
Glucose Transport Proteins
Life Sciences & Biomedicine
Statistics (Mathematics)
Human
Research Article
VARIANCES
Adult
PENETRANCE
GENES
lcsh:QH426-470
Evolution
European Continental Ancestry Group
Single-nucleotide polymorphism
Biostatistics
Biology
Quantitative trait locus
Polymorphism, Single Nucleotide
White People
03 medical and health sciences
Genomic Imprinting
Potassium Channels, Tandem Pore Domain
Genetic
Behavior and Systematics
SDG 3 - Good Health and Well-being
Genetic linkage
GIANT Consortium
Genome-Wide Association Studies
Humans
Genetic Predisposition to Disease
Statistical Methods
Allele
Polymorphism
Molecular Biology
Ecology, Evolution, Behavior and Systematics
Gene Expression Regulation
Genome-Wide Association Study
Obesity
030304 developmental biology
0604 Genetics
Science & Technology
LINKAGE ANALYSIS
SLC2A10 protein
Biology and Life Sciences
Computational Biology
Facilitative
Genome Analysis
Ecology, Evolution, Behavior and Systematic
lcsh:Genetics
Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5]
3111 Biomedicine
Genomic imprinting
Mathematics
030217 neurology & neurosurgery
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 15537390 and 15537404
- Database :
- OpenAIRE
- Journal :
- Hoggart, C J, Venturini, G, Mangino, M, Gomez, F, Ascari, G, Zhao, J H, Teumer, A, Winkler, T W, Tšernikova, N, Luan, J, Mihailov, E, Ehret, G B, Zhang, W, Lamparter, D, Esko, T, Macé, A, Rüeger, S, Bochud, P-Y, Barcella, M, Dauvilliers, Y, Benyamin, B, Evans, D M, Hayward, C, Lopez, M F, Franke, L, Russo, A, Heid, I M, Salvi, E, Vendantam, S, Arking, D E, Boerwinkle, E, Chambers, J C, Fiorito, G, Grallert, H, Guarrera, S, Homuth, G, Huffman, J E, Porteous, D, Moradpour, D, Iranzo, A, Hebebrand, J, Kemp, J P, Lammers, G J, Aubert, V, Heim, M H, Martin, N G, Montgomery, G W, Peraita-Adrados, R & Santamaria, J & Hastie, N D 2014, ' Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index ', PLoS Genetics, vol. 10, no. 7, e1004508 . https://doi.org/10.1371/journal.pgen.1004508, PLoS Genetics, PLoS genetics, 10(7):1004508. PUBLIC LIBRARY SCIENCE, PLoS Genetics, 10(7):e1004508. Public Library of Science, PLoS genetics, PLoS Genetics, vol. 10, no. 7, pp. e1004508, Hoggart, C J, Venturini, G, Mangino, M, Gomez, F, Ascari, G, Hottenga, J J, Willemsen, G, Boomsma, D I, Penninx, B W J H, Uitterlinden, A G, van Duijn, C M, Visscher, P M, Rousson, V, Hirschhorn, J N, Rivolta, C, Loos, R J F & Kutali, Z 2014, ' Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index ', PLoS Genetics, vol. 10, no. 7, e1004508 . https://doi.org/10.1371/journal.pgen.1004508, PLoS Genetics, Vol 10, Iss 7, p e1004508 (2014), PLoS genetics, 10(7). Public Library of Science, Plos Genetics, 10, 7, pp. e1004508, PLoS Genet. 10, 1-12:e1004508 (2014), PLOS GENETICS, Plos Genetics, 10, e1004508, PLOS Genetics, Vol. 10, No 7 (2014) P. e1004508
- Accession number :
- edsair.doi.dedup.....f16ecff53fa31003d93a4f0c6c3e21ce