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

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 ge... Full description

Journal Title: PLoS genetics July 2014, Vol.10(7), p.e1004508
Main Author: Hoggart, Clive J
Other Authors: 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
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1553-7404 ; DOI: 10.1371/journal.pgen.1004508
Link: http://search.proquest.com/docview/1551018781/?pq-origsite=primo
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title: Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.
format: Article
creator:
  • 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
subjects:
  • Adult–Genetics
  • Body Mass Index–Genetics
  • European Continental Ancestry Group–Genetics
  • Female–Pathology
  • Gene Expression Regulation–Genetics
  • Genetic Predisposition to Disease–Genetics
  • Genome-Wide Association Study–Genetics
  • Genomic Imprinting–Genetics
  • Genotype–Genetics
  • Glucose Transport Proteins, Facilitative–Genetics
  • Humans–Genetics
  • Male–Genetics
  • Obesity–Genetics
  • Polymorphism, Single Nucleotide–Genetics
  • Potassium Channels, Tandem Pore Domain–Genetics
  • Glucose Transport Proteins, Facilitative
  • Kcnk9 Protein, Human
  • Potassium Channels, Tandem Pore Domain
  • Slc2a10 Protein, Human
ispartof: PLoS genetics, July 2014, Vol.10(7), p.e1004508
description: 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
language: eng
source:
identifier: E-ISSN: 1553-7404 ; DOI: 10.1371/journal.pgen.1004508
fulltext: fulltext
issn:
  • 15537404
  • 1553-7404
url: Link


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titleNovel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.
creatorHoggart, 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
contributorGeleijnse, M (correspondence author) ; Harst, P V D (record owner) ; Koppelman, G ; Rosmalen, J G M ; van Rossum, L ; Smidt, H ; Swertz, M A ; Stolk, R P ; Alizadeh, B ; de Boer, R ; Boezen, H M ; Bruinenberg, M ; Franke, L ; van Der Harst, P ; Hillege, H ; van Der Klauw, M ; Navis, G ; Ormel, J ; Postma, D ; Rosmalen
ispartofPLoS genetics, July 2014, Vol.10(7), p.e1004508
identifierE-ISSN: 1553-7404 ; DOI: 10.1371/journal.pgen.1004508
subjectAdult–Genetics ; Body Mass Index–Genetics ; European Continental Ancestry Group–Genetics ; Female–Pathology ; Gene Expression Regulation–Genetics ; Genetic Predisposition to Disease–Genetics ; Genome-Wide Association Study–Genetics ; Genomic Imprinting–Genetics ; Genotype–Genetics ; Glucose Transport Proteins, Facilitative–Genetics ; Humans–Genetics ; Male–Genetics ; Obesity–Genetics ; Polymorphism, Single Nucleotide–Genetics ; Potassium Channels, Tandem Pore Domain–Genetics ; Glucose Transport Proteins, Facilitative ; Kcnk9 Protein, Human ; Potassium Channels, Tandem Pore Domain ; Slc2a10 Protein, Human
languageeng
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descriptionThe 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. 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.
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1Venturini, Giulia
2Mangino, Massimo
3Gomez, Felicia
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5Zhao, Jing Hua
6Teumer, Alexander
7Winkler, Thomas W
8Tšernikova, Natalia
9Luan, Jian'an
10Mihailov, Evelin
11Ehret, Georg B
12Zhang, Weihua
13Lamparter, David
14Esko, Tõnu
15Macé, Aurelien
16Rüeger, Sina
17Bochud, Pierre-Yves
18Barcella, Matteo
19Dauvilliers, Yves
20Benyamin, Beben
21Evans, David M
22Hayward, Caroline
23Lopez, Mary F
24Franke, Lude
25Russo, Alessia
26Heid, Iris M
27Salvi, Erika
28Vendantam, Sailaja
29Arking, Dan E
30Boerwinkle, Eric
31Chambers, John C
32Fiorito, Giovanni
33Grallert, Harald
34Guarrera, Simonetta
35Homuth, Georg
36Huffman, Jennifer E
37Porteous, David
38Moradpour, Darius
39Iranzo, Alex
40Hebebrand, Johannes
41Kemp, John P
42Lammers, Gert J
43Aubert, Vincent
44Heim, Markus H
45Martin, Nicholas G
46Montgomery, Grant W
47Peraita-Adrados, Rosa
48Santamaria, Joan
49Negro, Francesco
50Schmidt, Carsten O
51Scott, Robert A
52Spector, Tim D
53Strauch, Konstantin
54Völzke, Henry
55Wareham, Nicholas J
56Yuan, Wei
57Bell, Jordana T
58Chakravarti, Aravinda
59Kooner, Jaspal S
60Peters, Annette
61Matullo, Giuseppe
62Wallaschofski, Henri
63Whitfield, John B
64Paccaud, Fred
65Vollenweider, Peter
66Bergmann, Sven
67Beckmann, Jacques S
68Tafti, Mehdi
69Hastie, Nicholas D
70Cusi, Daniele
71Bochud, Murielle
72Frayling, Timothy M
73Metspalu, Andres
74Jarvelin, Marjo-Riitta
75Scherag, André
76Smith, George Davey
77Borecki, Ingrid B
78Rousson, Valentin
79Hirschhorn, Joel N
80Rivolta, Carlo
81Loos, Ruth J F
82Kutalik, Zoltán
83de Bakker, P
84Bültmann, U
titleNovel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.
subject
0Adult–Genetics
1Body Mass Index–Genetics
2European Continental Ancestry Group–Genetics
3Female–Pathology
4Gene Expression Regulation–Genetics
5Genetic Predisposition to Disease–Genetics
6Genome-Wide Association Study–Genetics
7Genomic Imprinting–Genetics
8Genotype–Genetics
9Glucose Transport...
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4van Rossum, L
5Smidt, H
6Swertz, M A
7Stolk, R P
8Alizadeh, B
9de Boer, R
10Boezen, H M
11Bruinenberg, M
12Franke, L
13van Der Harst, P
14Hillege, H
15van Der Klauw, M
16Navis, G
17Ormel, J
18Postma, D
19Rosmalen, J
20Slaets, J
21Snieder, H
22Stolk, R
23Wolffenbuttel, B
24Wijmenga, C
25Berg, Jonathan
26Blackwood, Douglas
27Campbell, Harry
28Cavanagh, Jonathan
29Connell, John
30Connor, Mike
31Cunningham-Burley, Sarah
32Deary, Ian
33Dominiczak, Anna
34Ellis, Paul
35Fitzpatrick, Bridie
36Ford, Ian
37Gertz, Rena
38Grau, Antonio
39Haddow, Gill
40Jackson, Cathy
41Kerr, Shona
42Lindsay, Robbie
43Mcgilchrist, Mark
44Mcintyre, Donald
45Morris, Andrew
46Morton, Robin
47Muir, Walter
48Murray, Graeme
49Palmer, Colin
50Pell, Jill
51Philp, Alastair
52Porteous, David
53Porteous, Mary
54Procter, Rob
55Ralston, Stuart
56Reid, David
57Sinnott, Richard
58Smith, Blair
59Clair, David St
60Sullivan, Frank
61Sweetland, Mary
62Ure, Jenny
63Watt, Graham
64Wolf, Roland
65Wright, Alan
66Berndt, Sonja I
67Gustafsson, Stefan
68Mägi, Reedik
69Ganna, Andrea
70Wheeler, Eleanor
71Feitosa, Mary F
72Justice, Anne E
73Monda, Keri L
74Croteau- Chonka, Damien C
75Day, Felix R
76Esko, Tonu
77Fall, Tove
78Ferreira, Teresa
79Gentilini, Davide
80Jackson, Anne U
81Luan, Jian'an
82Randall, Joshua C
83Vedantam, Sailaja
84Willer, Cristen J
85Winkler, Thomas W
86Wood, Andrew R
87Workalemahu, Tsegaselassie
88Hu, Yi-Juan
89Lee, Sang Hong
90Liang, Liming
91Lin, Dan-Yu
92Min, Josine L
93Neale, Benjamin M
94Thorleifsson, Gudmar
95Yang, Jian
96Albrecht, Eva
97Amin, Najaf
98Bragg-Gresham, Jennifer L
99Cadby, Gemma
100...
startdate20140701
enddate20140701
citationpf e1004508 pt e1004508 vol 10 issue 7
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titleNovel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.
authorHoggart, 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
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1Body Mass Index–Genetics
2European Continental Ancestry Group–Genetics
3Female–Pathology
4Gene Expression Regulation–Genetics
5Genetic Predisposition to Disease–Genetics
6Genome-Wide Association Study–Genetics
7Genomic Imprinting–Genetics
8Genotype–Genetics
9Glucose Transport...
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1Venturini, Giulia
2Mangino, Massimo
3Gomez, Felicia
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5Zhao, Jing Hua
6Teumer, Alexander
7Winkler, Thomas W
8Tšernikova, Natalia
9Luan, Jian'an
10Mihailov, Evelin
11Ehret, Georg B
12Zhang, Weihua
13Lamparter, David
14Esko, Tõnu
15Macé, Aurelien
16Rüeger, Sina
17Bochud, Pierre-Yves
18Barcella, Matteo
19Dauvilliers, Yves
20Benyamin, Beben
21Evans, David M
22Hayward, Caroline
23Lopez, Mary F
24Franke, Lude
25Russo, Alessia
26Heid, Iris M
27Salvi, Erika
28Vendantam, Sailaja
29Arking, Dan E
30Boerwinkle, Eric
31Chambers, John C
32Fiorito, Giovanni
33Grallert, Harald
34Guarrera, Simonetta
35Homuth, Georg
36Huffman, Jennifer E
37Porteous, David
38Moradpour, Darius
39Iranzo, Alex
40Hebebrand, Johannes
41Kemp, John P
42Lammers, Gert J
43Aubert, Vincent
44Heim, Markus H
45Martin, Nicholas G
46Montgomery, Grant W
47Peraita-Adrados, Rosa
48Santamaria, Joan
49Negro, Francesco
50Schmidt, Carsten O
51Scott, Robert A
52Spector, Tim D
53Strauch, Konstantin
54Völzke, Henry
55Wareham, Nicholas J
56Yuan, Wei
57Bell, Jordana T
58Chakravarti, Aravinda
59Kooner, Jaspal S
60Peters, Annette
61Matullo, Giuseppe
62Wallaschofski, Henri
63Whitfield, John B
64Paccaud, Fred
65Vollenweider, Peter
66Bergmann, Sven
67Beckmann, Jacques S
68Tafti, Mehdi
69Hastie, Nicholas D
70Cusi, Daniele
71Bochud, Murielle
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73Metspalu, Andres
74Jarvelin, Marjo-Riitta
75Scherag, André
76Smith, George Davey
77Borecki, Ingrid B
78Rousson, Valentin
79Hirschhorn, Joel N
80Rivolta, Carlo
81Loos, Ruth J F
82Kutalik, Zoltán
83de Bakker, P
84Bültmann, U
85Geleijnse, M
86Harst, P V D
87Koppelman, G
88Rosmalen, J G M
89van Rossum, L
90Smidt, H
91Swertz, M A
92Stolk, R P
93Alizadeh, B
94de Boer, R
95Boezen, H M
96Bruinenberg, M
97Franke, L
98van Der Harst, P
99Hillege, H
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1Venturini, Giulia
2Mangino, Massimo
3Gomez, Felicia
4Ascari, Giulia
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8Tšernikova, Natalia
9Luan, Jian'an
10Mihailov, Evelin
11Ehret, Georg B
12Zhang, Weihua
13Lamparter, David
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15Macé, Aurelien
16Rüeger, Sina
17Bochud, Pierre-Yves
18Barcella, Matteo
19Dauvilliers, Yves
20Benyamin, Beben
21Evans, David M
22Hayward, Caroline
23Lopez, Mary F
24Franke, Lude
25Russo, Alessia
26Heid, Iris M
27Salvi, Erika
28Vendantam, Sailaja
29Arking, Dan E
30Boerwinkle, Eric
31Chambers, John C
32Fiorito, Giovanni
33Grallert, Harald
34Guarrera, Simonetta
35Homuth, Georg
36Huffman, Jennifer E
37Porteous, David
38Moradpour, Darius
39Iranzo, Alex
40Hebebrand, Johannes
41Kemp, John P
42Lammers, Gert J
43Aubert, Vincent
44Heim, Markus H
45Martin, Nicholas G
46Montgomery, Grant W
47Peraita-Adrados, Rosa
48Santamaria, Joan
49Negro, Francesco
50Schmidt, Carsten O
51Scott, Robert A
52Spector, Tim D
53Strauch, Konstantin
54Völzke, Henry
55Wareham, Nicholas J
56Yuan, Wei
57Bell, Jordana T
58Chakravarti, Aravinda
59Kooner, Jaspal S
60Peters, Annette
61Matullo, Giuseppe
62Wallaschofski, Henri
63Whitfield, John B
64Paccaud, Fred
65Vollenweider, Peter
66Bergmann, Sven
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68Tafti, Mehdi
69Hastie, Nicholas D
70Cusi, Daniele
71Bochud, Murielle
72Frayling, Timothy M
73Metspalu, Andres
74Jarvelin, Marjo-Riitta
75Scherag, André
76Smith, George Davey
77Borecki, Ingrid B
78Rousson, Valentin
79Hirschhorn, Joel N
80Rivolta, Carlo
81Loos, Ruth J F
82Kutalik, Zoltán
83de Bakker, P
84Bültmann, U
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1Harst, P v d
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3Rosmalen, J G M
4van Rossum, L
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8Alizadeh, B
9de Boer, R
10Boezen, H M
11Bruinenberg, M
12Franke, L
13van der Harst, P
14Hillege, H
15van der Klauw, M
16Navis, G
17Ormel, J
18Postma, D
19Rosmalen, J
20Slaets, J
21Snieder, H
22Stolk, R
23Wolffenbuttel, B
24Wijmenga, C
25Berg, Jonathan
26Blackwood, Douglas
27Campbell, Harry
28Cavanagh, Jonathan
29Connell, John
30Connor, Mike
31Cunningham-Burley, Sarah
32Deary, Ian
33Dominiczak, Anna
34Ellis, Paul
35FitzPatrick, Bridie
36Ford, Ian
37Gertz, Rena
38Grau, Antonio
39Haddow, Gill
40Jackson, Cathy
41Kerr, Shona
42Lindsay, Robbie
43McGilchrist, Mark
44McIntyre, Donald
45Morris, Andrew
46Morton, Robin
47Muir, Walter
48Murray, Graeme
49Palmer, Colin
50Pell, Jill
51Philp, Alastair
52Porteous, David
53Porteous, Mary
54Procter, Rob
55Ralston, Stuart
56Reid, David
57Sinnott, Richard
58Smith, Blair
59Clair, David St
60Sullivan, Frank
61Sweetland, Mary
62Ure, Jenny
63Watt, Graham
64Wolf, Roland
65Wright, Alan
66Berndt, Sonja I
67Gustafsson, Stefan
68Mägi, Reedik
69Ganna, Andrea
70Wheeler, Eleanor
71Feitosa, Mary F
72Justice, Anne E
73Monda, Keri L
74Croteau- Chonka, Damien C
75Day, Felix R
76Esko, Tonu
77Fall, Tove
78Ferreira, Teresa
79Gentilini, Davide
80Jackson, Anne U
81Luan, Jian'an
82Randall, Joshua C
83Vedantam, Sailaja
84Willer, Cristen J
85Winkler, Thomas W
86Wood, Andrew R
87Workalemahu, Tsegaselassie
88Hu, Yi-Juan
89Lee, Sang Hong
90Liang, Liming
91Lin, Dan-Yu
92Min, Josine L
93Neale, Benjamin M
94Thorleifsson, Gudmar
95Yang, Jian
96Albrecht, Eva
97Amin, Najaf
98Bragg-Gresham, Jennifer L
99Cadby, Gemma
100...
atitleNovel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.
jtitlePLoS genetics
risdate20140701
volume10
issue7
spagee1004508
epagee1004508
pagese1004508
eissn1553-7404
formatjournal
genrearticle
ristypeJOUR
doi10.1371/journal.pgen.1004508
urlhttp://search.proquest.com/docview/1551018781/
issn15537390
date2014-07-01