The University of Southampton
University of Southampton Institutional Repository

Common variants near MC4R are associated with fat mass, weight and risk of obesity

Common variants near MC4R are associated with fat mass, weight and risk of obesity
Common variants near MC4R are associated with fat mass, weight and risk of obesity
To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits
1061-4036
768-775
Loos, Ruth J.F.
39429771-c022-48b0-ba13-54cefb98ad77
Lindgren, Cecilia M.
0f22a7b8-b8ed-494c-a7d2-f93c667ac40d
Li, Shengxu
f41f3f13-8f87-4402-823d-eebeec5c4060
Wheeler, Eleanor
7ac224f8-8891-4365-9741-0f08b27d233a
Zhao, Jing Hua
b79522c0-ea16-4dd1-8405-cec85df7b9f5
Prokopenko, Inga
e56ceffd-52b1-4503-ac82-adc537595e6e
Inouye, Michael
17fed1bc-6082-41e9-8807-e8e7d455d29d
Freathy, Rachel M.
1fd3aeab-3581-4fc8-9c85-a174cd15c9db
Attwood, Antony P.
40b6be67-ac85-49a2-aa11-c41878896cea
Beckmann, Jacques S.
3880c216-3f63-4b08-bf61-8542ebcf680d
Berndt, Sonja I.
98d42dc2-4308-4f9d-b18b-0a5682cef839
Jacobs, Kevin B.
88f573f4-96e6-40fb-aa6a-65969de0247f
Chanock, Stephen J.
aedc4433-6ad0-4283-ba53-315c9b77c047
Hayes, Richard B.
c122ebf9-a4da-40cc-bcac-80ac52419c4d
Bergmann, Sven
c452e4ba-e86a-4243-9714-59ac29d45410
Bennett, Amanda J.
332c940b-1d17-4c28-b451-91223aa163f7
Bingham, Sheila A.
1e0cc4a8-d340-4794-bf19-72f35b69beb6
Bochud, Murielle
3d5c3af3-a1d3-422a-b803-cdfdd89406a7
Brown, Morris
80403c58-0155-49ad-bf94-bf57f68665b5
Cauchi, Stephane
abe2704b-c70b-4d84-b827-ab4a81f53653
Connell, John M.
08c5a11f-6336-4438-a436-a9d40d1fe43b
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Smith, George Davey
f5bc8327-f2cb-49a0-8eae-4a6ba63207a2
Day, Ian
dd32ab24-2ffc-435e-be2d-9fbb46055ae3
Dina, Christian
3df025f2-1369-4ea6-84a3-f58994951f68
De, Subhayoti
758d2a57-e2a5-4682-945a-211190c63055
Dermitzakis, Emmanouil T.
96ab825e-9a4e-4d8f-9930-0c551dd34f27
Doney, Alex S.F.
ac3d4823-7d6c-4728-9523-c6c98dc19c7f
Elliott, Katherine S.
85438fff-d52d-4961-9d8e-5f5a65ba097b
Elliott, Paul
5e19ee8c-f18a-417e-ad53-bc807fdfd191
Evans, David M.
7adf29d1-837e-4c60-8e1c-247dc8e3b68b
Farooqi, I.Sadaf
e96b7978-30ac-46dd-9315-7d0924dabea5
Froguel, Phillipe
5813a243-d7c0-4377-889d-bcb16c8af7ef
Ghori, Jilur
e48fb936-b094-4a57-b541-a92b8f74441e
Groves, Christopher J.
926eb851-056c-446a-b1bd-04008c21a3da
Gwilliam, Rhian
71dda979-6126-4d76-9789-d109b266cbfb
Hadley, David
14dbcc2f-8180-4329-977c-7acf11e95af5
Hall, Alistair S.
c2861d32-b385-4fe9-9559-1562ca7b869c
Hattersley, A. T. J.
4b0b1cf0-b11c-442a-9107-d94768bf7e7e
Heid, Iris M.
166665f0-ed45-4d07-9019-4f7e933df873
Lamina, Claudia
ff0247b6-9f2e-4854-b0bb-b907755d00dc
Gieger, Christian
45f48b74-8ab8-4be6-ad54-91e61163ed5e
Illig, Thomas
44bc21a8-d516-45b6-b5e8-a259ef91626a
Meitinger, Thomas
cee5677e-e82d-4212-a028-acc602ad0378
Wichmann, H-Erich
4628c10c-ff92-4eae-9ee8-7122efa70425
Herrera, Blanca
ce0f3935-3790-4109-a9e6-11bcf6a94796
Hinney, Anke
5af942fb-7f85-420c-8b32-d44b49d71494
Hunt, Sarah E.
c5789063-1e2b-474d-a80d-d9fbe6b7707c
Jarvelin, Manjo-Riitta
2db98df0-3a4f-450e-9a21-28a64f37307f
Johnson, Toby
bfc52812-3179-4a21-ba30-6353dcc122c2
Jolley, Jennifer D.M.
480a192d-eaf3-49f4-b269-e453aba0edeb
Karpe, Fredrik
05abcb32-83b7-44eb-ab12-7c360f4f9c12
Keniry, Andrew
7c90c306-a850-4f38-9a70-58cee8fd347c
Khaw, Kay-Tee
b17eadde-5721-45e8-8bf5-ac048db9fb44
Luben, Robert N.
ce4b7673-9cf6-420f-a78f-5c4b74ae5ed5
Mangino, Massimo
19ad1660-3639-45a8-93d6-e6a9b5c1c64b
Marchini, Jonathan
e98649d0-f4b6-4295-80e2-2eee6a97fc4e
McArdle, Wendy L.
986afcf6-20a0-4825-9ede-030b274e594c
McGinnis, Ralph
7e1751d6-adb5-442c-8d90-a89f29c44344
Meyre, David
023f567d-798c-41f0-a096-2028569a3976
Munroe, Patricia B.
44d23746-20cd-4572-860e-7350424cc031
Morris, Andrew D.
f8dd17be-9a38-4a8b-9102-b0d8a423e15f
Ness, Andrew R.
0e39b68f-1484-44bd-ac49-297a8d7f4597
Neville, Matthew J.
b7c9383b-0713-4c97-9d84-cb79ebde7949
Nica, A.lexandra C.
c00f1fbd-1dc7-4d1c-99a5-1824d0a4c662
Ong, Ken K.
11be427c-95c2-4c09-9000-2a915a247885
O'Rahilly, Stephen
e5c7869f-10d1-4fdc-a564-e4907be415a3
Owen, Katharine R.
b7373528-92e5-4652-85d4-f29a446b994b
Palmer, Colin N.
22dd8790-79f1-4cdd-a10e-c5eae74c9d27
Papadakis, Konstantinos
7feeffc5-873e-4add-b5de-061655898730
Potter, Simon
b717330b-5498-4719-abbb-22892f681bda
Pouta, Anneli
108c5aa1-3b41-4095-91fa-ecd523934370
Qi, Lu
724df082-7f58-4d88-a859-2bf8464b29f4
Randall, Joshua C.
fecaa08a-f6ea-4b00-9373-5cf145653506
Rayner, Nigel W.
d356f031-ef87-4aca-8ed6-9ffe329a2dbc
Ring, Susan M.
55bebe97-d035-43f3-84a6-b57c5ea4c6be
Sandhu, Manjinder S.
02fcd83e-4a42-45cf-93e6-1e522d29dbdb
Scherag, Andre
d630d41f-92e9-44c2-a5de-97d77e49f8e3
Sims, Mathew A.
e2e03dcd-fe85-4ffb-bd49-605be4a0f40e
Song, Kijoung
1ab872a2-8946-408e-8417-7740e3717add
Soranzo, Nicole
959629a3-c46e-46c2-93b3-720e66e04fb0
Speliotes, Elizabeth K.
89e193f2-01b9-4779-8d48-6d168a56c4e3
Syddall, Holly E.
a0181a93-8fc3-4998-a996-7963f0128328
Teichmann, Sarah A.
e72b3afe-69c5-46f5-a47c-ec53edd23a52
Timpson, Nicholas J.
ef38d847-22ec-4030-99cb-e77986b0815d
Tobias, Jonathan H.
514342d7-3491-4a7b-bbeb-b00dcf244daa
Uda, Manuela
3155e673-0010-484e-9689-e2cb528496dd
Ganz Vogel, Carla I.
392f8be4-9fc6-4da5-a123-d8e9b508ac6f
Wallace, Chris
3c619a52-12bd-4df0-9dbf-97611bc00abb
Waterworth, Dawn M.
1a110a48-1069-4678-a67e-f8f6ea24a662
Weedon, Michael N.
4ea46048-ef8b-4052-8ff6-a40cf8f5a913
Willer, Cristen J.
25dd7a8a-6644-4476-803a-8b5f46c8fdb1
Wraight, Vicki L
be9d6a94-7eaa-480e-887c-f4e880e0b96c
Zeggini, Eleftheria
b487a5f2-c446-4d9b-b964-9ff8823074ff
Hirschhorn, Joel N.
a034b496-b6e5-47f5-85f1-e88a068201b9
Strachan, David P.
76ddbacc-b6cb-48db-8ab6-77f799c8d1c8
Caulfield, Mark J.
a13960ad-3f25-453e-a127-2913a935d73a
Samani, Nilesh J.
548b29ab-a422-4827-a9c6-5db0e6cf8ae6
Frayling, Timothy M.
ddaaa2c7-b281-4c60-a8d8-8f4657d46974
Vollenweider, Peter
c99f7359-b098-46a4-b292-a31c35b9a0c9
Waeber, Gerard
fbf763e4-ebbb-4ad8-9529-cb41dee27e56
Mooser, Vincent
746da18f-c985-496c-af27-4e25221635b3
Deloukas, Panos
f8c385df-85e0-4769-9a5b-aaf03ec01d1f
McCarthy, Mark I.
ff42236d-bc18-406f-898b-d10ce8d0bab2
Wareham, Nicholas J.
bbc18cd9-3512-4ca6-806c-75c9a01e5adf
Barroso, Ines
42fd48c7-aac6-4204-8f15-50df92a1a7ce
Kraft, Peter
56e8fc90-2229-4abc-9d9b-7c4e3a934832
Hankinson, Susan E.
8bbef186-0f58-4868-bed9-c933e068d984
Hunter, David J.
2a7b7bbf-a9cc-4a70-8d2a-fbb169501a14
Hu, Frank B.
f1df4397-9bd2-4705-bdca-12da97caffd2
Lyon, Helen N.
e870f687-9bee-4b9e-96d2-ce3bdf3fbea1
Voight, Benjamin F.
713b8fa6-db45-46c3-8212-775255feda55
Ridderstrale, Midderstrale
4bd724f8-79eb-40bb-a70a-8e8aa4eb97c2
Groop, Leif
4f7742e5-1170-4a82-8919-dde38619c7a8
Scheet, Paul
f5d5fd7e-6f04-4695-b65b-a66c2d2f7090
Sanna, Serena
0a8113f9-09f9-4669-8cf7-48b0c6957c7b
Abecasis, Goncalo R.
7e146050-10b1-4981-8de8-ae3607b3852a
Albai, Giuseppe
b0f1c959-deb7-495f-89eb-fcd379fccf88
Nagaraja, Ramaiah
0a2b0b96-1b2c-4b7f-a9a4-1135f541402e
Schlessinger, David
b1b9602b-af46-406a-92d9-0dfad2c8047d
Jackson, Anne U.
c5f3a446-5145-4a5a-8b09-78364439a9a0
Tuomilehto, Jaakko
60f9ac84-bbfd-43a1-91a8-25415c36dfb1
Collins, Francis S.
c02a6ec0-8495-4776-aff4-d17151a0d22c
Boehnke, Michael
5a29254d-7869-4848-9673-70f0d24c0964
Mohlke, Karen L
5f328077-6cb0-46cd-85de-2d8b0a8aeaa3
Hebebrand, Johannes
4fd93285-3e62-4e60-b7f8-ff565dea7ae7
Yuan, Xin
79345c17-417d-4aae-87b3-924e281775e6
Ouwehand, Willem H.
00fa6721-1d9e-4b4b-8644-f823e37e04fc
Loos, Ruth J.F.
39429771-c022-48b0-ba13-54cefb98ad77
Lindgren, Cecilia M.
0f22a7b8-b8ed-494c-a7d2-f93c667ac40d
Li, Shengxu
f41f3f13-8f87-4402-823d-eebeec5c4060
Wheeler, Eleanor
7ac224f8-8891-4365-9741-0f08b27d233a
Zhao, Jing Hua
b79522c0-ea16-4dd1-8405-cec85df7b9f5
Prokopenko, Inga
e56ceffd-52b1-4503-ac82-adc537595e6e
Inouye, Michael
17fed1bc-6082-41e9-8807-e8e7d455d29d
Freathy, Rachel M.
1fd3aeab-3581-4fc8-9c85-a174cd15c9db
Attwood, Antony P.
40b6be67-ac85-49a2-aa11-c41878896cea
Beckmann, Jacques S.
3880c216-3f63-4b08-bf61-8542ebcf680d
Berndt, Sonja I.
98d42dc2-4308-4f9d-b18b-0a5682cef839
Jacobs, Kevin B.
88f573f4-96e6-40fb-aa6a-65969de0247f
Chanock, Stephen J.
aedc4433-6ad0-4283-ba53-315c9b77c047
Hayes, Richard B.
c122ebf9-a4da-40cc-bcac-80ac52419c4d
Bergmann, Sven
c452e4ba-e86a-4243-9714-59ac29d45410
Bennett, Amanda J.
332c940b-1d17-4c28-b451-91223aa163f7
Bingham, Sheila A.
1e0cc4a8-d340-4794-bf19-72f35b69beb6
Bochud, Murielle
3d5c3af3-a1d3-422a-b803-cdfdd89406a7
Brown, Morris
80403c58-0155-49ad-bf94-bf57f68665b5
Cauchi, Stephane
abe2704b-c70b-4d84-b827-ab4a81f53653
Connell, John M.
08c5a11f-6336-4438-a436-a9d40d1fe43b
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Smith, George Davey
f5bc8327-f2cb-49a0-8eae-4a6ba63207a2
Day, Ian
dd32ab24-2ffc-435e-be2d-9fbb46055ae3
Dina, Christian
3df025f2-1369-4ea6-84a3-f58994951f68
De, Subhayoti
758d2a57-e2a5-4682-945a-211190c63055
Dermitzakis, Emmanouil T.
96ab825e-9a4e-4d8f-9930-0c551dd34f27
Doney, Alex S.F.
ac3d4823-7d6c-4728-9523-c6c98dc19c7f
Elliott, Katherine S.
85438fff-d52d-4961-9d8e-5f5a65ba097b
Elliott, Paul
5e19ee8c-f18a-417e-ad53-bc807fdfd191
Evans, David M.
7adf29d1-837e-4c60-8e1c-247dc8e3b68b
Farooqi, I.Sadaf
e96b7978-30ac-46dd-9315-7d0924dabea5
Froguel, Phillipe
5813a243-d7c0-4377-889d-bcb16c8af7ef
Ghori, Jilur
e48fb936-b094-4a57-b541-a92b8f74441e
Groves, Christopher J.
926eb851-056c-446a-b1bd-04008c21a3da
Gwilliam, Rhian
71dda979-6126-4d76-9789-d109b266cbfb
Hadley, David
14dbcc2f-8180-4329-977c-7acf11e95af5
Hall, Alistair S.
c2861d32-b385-4fe9-9559-1562ca7b869c
Hattersley, A. T. J.
4b0b1cf0-b11c-442a-9107-d94768bf7e7e
Heid, Iris M.
166665f0-ed45-4d07-9019-4f7e933df873
Lamina, Claudia
ff0247b6-9f2e-4854-b0bb-b907755d00dc
Gieger, Christian
45f48b74-8ab8-4be6-ad54-91e61163ed5e
Illig, Thomas
44bc21a8-d516-45b6-b5e8-a259ef91626a
Meitinger, Thomas
cee5677e-e82d-4212-a028-acc602ad0378
Wichmann, H-Erich
4628c10c-ff92-4eae-9ee8-7122efa70425
Herrera, Blanca
ce0f3935-3790-4109-a9e6-11bcf6a94796
Hinney, Anke
5af942fb-7f85-420c-8b32-d44b49d71494
Hunt, Sarah E.
c5789063-1e2b-474d-a80d-d9fbe6b7707c
Jarvelin, Manjo-Riitta
2db98df0-3a4f-450e-9a21-28a64f37307f
Johnson, Toby
bfc52812-3179-4a21-ba30-6353dcc122c2
Jolley, Jennifer D.M.
480a192d-eaf3-49f4-b269-e453aba0edeb
Karpe, Fredrik
05abcb32-83b7-44eb-ab12-7c360f4f9c12
Keniry, Andrew
7c90c306-a850-4f38-9a70-58cee8fd347c
Khaw, Kay-Tee
b17eadde-5721-45e8-8bf5-ac048db9fb44
Luben, Robert N.
ce4b7673-9cf6-420f-a78f-5c4b74ae5ed5
Mangino, Massimo
19ad1660-3639-45a8-93d6-e6a9b5c1c64b
Marchini, Jonathan
e98649d0-f4b6-4295-80e2-2eee6a97fc4e
McArdle, Wendy L.
986afcf6-20a0-4825-9ede-030b274e594c
McGinnis, Ralph
7e1751d6-adb5-442c-8d90-a89f29c44344
Meyre, David
023f567d-798c-41f0-a096-2028569a3976
Munroe, Patricia B.
44d23746-20cd-4572-860e-7350424cc031
Morris, Andrew D.
f8dd17be-9a38-4a8b-9102-b0d8a423e15f
Ness, Andrew R.
0e39b68f-1484-44bd-ac49-297a8d7f4597
Neville, Matthew J.
b7c9383b-0713-4c97-9d84-cb79ebde7949
Nica, A.lexandra C.
c00f1fbd-1dc7-4d1c-99a5-1824d0a4c662
Ong, Ken K.
11be427c-95c2-4c09-9000-2a915a247885
O'Rahilly, Stephen
e5c7869f-10d1-4fdc-a564-e4907be415a3
Owen, Katharine R.
b7373528-92e5-4652-85d4-f29a446b994b
Palmer, Colin N.
22dd8790-79f1-4cdd-a10e-c5eae74c9d27
Papadakis, Konstantinos
7feeffc5-873e-4add-b5de-061655898730
Potter, Simon
b717330b-5498-4719-abbb-22892f681bda
Pouta, Anneli
108c5aa1-3b41-4095-91fa-ecd523934370
Qi, Lu
724df082-7f58-4d88-a859-2bf8464b29f4
Randall, Joshua C.
fecaa08a-f6ea-4b00-9373-5cf145653506
Rayner, Nigel W.
d356f031-ef87-4aca-8ed6-9ffe329a2dbc
Ring, Susan M.
55bebe97-d035-43f3-84a6-b57c5ea4c6be
Sandhu, Manjinder S.
02fcd83e-4a42-45cf-93e6-1e522d29dbdb
Scherag, Andre
d630d41f-92e9-44c2-a5de-97d77e49f8e3
Sims, Mathew A.
e2e03dcd-fe85-4ffb-bd49-605be4a0f40e
Song, Kijoung
1ab872a2-8946-408e-8417-7740e3717add
Soranzo, Nicole
959629a3-c46e-46c2-93b3-720e66e04fb0
Speliotes, Elizabeth K.
89e193f2-01b9-4779-8d48-6d168a56c4e3
Syddall, Holly E.
a0181a93-8fc3-4998-a996-7963f0128328
Teichmann, Sarah A.
e72b3afe-69c5-46f5-a47c-ec53edd23a52
Timpson, Nicholas J.
ef38d847-22ec-4030-99cb-e77986b0815d
Tobias, Jonathan H.
514342d7-3491-4a7b-bbeb-b00dcf244daa
Uda, Manuela
3155e673-0010-484e-9689-e2cb528496dd
Ganz Vogel, Carla I.
392f8be4-9fc6-4da5-a123-d8e9b508ac6f
Wallace, Chris
3c619a52-12bd-4df0-9dbf-97611bc00abb
Waterworth, Dawn M.
1a110a48-1069-4678-a67e-f8f6ea24a662
Weedon, Michael N.
4ea46048-ef8b-4052-8ff6-a40cf8f5a913
Willer, Cristen J.
25dd7a8a-6644-4476-803a-8b5f46c8fdb1
Wraight, Vicki L
be9d6a94-7eaa-480e-887c-f4e880e0b96c
Zeggini, Eleftheria
b487a5f2-c446-4d9b-b964-9ff8823074ff
Hirschhorn, Joel N.
a034b496-b6e5-47f5-85f1-e88a068201b9
Strachan, David P.
76ddbacc-b6cb-48db-8ab6-77f799c8d1c8
Caulfield, Mark J.
a13960ad-3f25-453e-a127-2913a935d73a
Samani, Nilesh J.
548b29ab-a422-4827-a9c6-5db0e6cf8ae6
Frayling, Timothy M.
ddaaa2c7-b281-4c60-a8d8-8f4657d46974
Vollenweider, Peter
c99f7359-b098-46a4-b292-a31c35b9a0c9
Waeber, Gerard
fbf763e4-ebbb-4ad8-9529-cb41dee27e56
Mooser, Vincent
746da18f-c985-496c-af27-4e25221635b3
Deloukas, Panos
f8c385df-85e0-4769-9a5b-aaf03ec01d1f
McCarthy, Mark I.
ff42236d-bc18-406f-898b-d10ce8d0bab2
Wareham, Nicholas J.
bbc18cd9-3512-4ca6-806c-75c9a01e5adf
Barroso, Ines
42fd48c7-aac6-4204-8f15-50df92a1a7ce
Kraft, Peter
56e8fc90-2229-4abc-9d9b-7c4e3a934832
Hankinson, Susan E.
8bbef186-0f58-4868-bed9-c933e068d984
Hunter, David J.
2a7b7bbf-a9cc-4a70-8d2a-fbb169501a14
Hu, Frank B.
f1df4397-9bd2-4705-bdca-12da97caffd2
Lyon, Helen N.
e870f687-9bee-4b9e-96d2-ce3bdf3fbea1
Voight, Benjamin F.
713b8fa6-db45-46c3-8212-775255feda55
Ridderstrale, Midderstrale
4bd724f8-79eb-40bb-a70a-8e8aa4eb97c2
Groop, Leif
4f7742e5-1170-4a82-8919-dde38619c7a8
Scheet, Paul
f5d5fd7e-6f04-4695-b65b-a66c2d2f7090
Sanna, Serena
0a8113f9-09f9-4669-8cf7-48b0c6957c7b
Abecasis, Goncalo R.
7e146050-10b1-4981-8de8-ae3607b3852a
Albai, Giuseppe
b0f1c959-deb7-495f-89eb-fcd379fccf88
Nagaraja, Ramaiah
0a2b0b96-1b2c-4b7f-a9a4-1135f541402e
Schlessinger, David
b1b9602b-af46-406a-92d9-0dfad2c8047d
Jackson, Anne U.
c5f3a446-5145-4a5a-8b09-78364439a9a0
Tuomilehto, Jaakko
60f9ac84-bbfd-43a1-91a8-25415c36dfb1
Collins, Francis S.
c02a6ec0-8495-4776-aff4-d17151a0d22c
Boehnke, Michael
5a29254d-7869-4848-9673-70f0d24c0964
Mohlke, Karen L
5f328077-6cb0-46cd-85de-2d8b0a8aeaa3
Hebebrand, Johannes
4fd93285-3e62-4e60-b7f8-ff565dea7ae7
Yuan, Xin
79345c17-417d-4aae-87b3-924e281775e6
Ouwehand, Willem H.
00fa6721-1d9e-4b4b-8644-f823e37e04fc

Loos, Ruth J.F., Lindgren, Cecilia M., Li, Shengxu, Wheeler, Eleanor, Zhao, Jing Hua, Prokopenko, Inga, Inouye, Michael, Freathy, Rachel M., Attwood, Antony P., Beckmann, Jacques S., Berndt, Sonja I., Jacobs, Kevin B., Chanock, Stephen J., Hayes, Richard B., Bergmann, Sven, Bennett, Amanda J., Bingham, Sheila A., Bochud, Murielle, Brown, Morris, Cauchi, Stephane, Connell, John M., Cooper, Cyrus, Smith, George Davey, Day, Ian, Dina, Christian, De, Subhayoti, Dermitzakis, Emmanouil T., Doney, Alex S.F., Elliott, Katherine S., Elliott, Paul, Evans, David M., Farooqi, I.Sadaf, Froguel, Phillipe, Ghori, Jilur, Groves, Christopher J., Gwilliam, Rhian, Hadley, David, Hall, Alistair S., Hattersley, A. T. J., Heid, Iris M., Lamina, Claudia, Gieger, Christian, Illig, Thomas, Meitinger, Thomas, Wichmann, H-Erich, Herrera, Blanca, Hinney, Anke, Hunt, Sarah E., Jarvelin, Manjo-Riitta, Johnson, Toby, Jolley, Jennifer D.M., Karpe, Fredrik, Keniry, Andrew, Khaw, Kay-Tee, Luben, Robert N., Mangino, Massimo, Marchini, Jonathan, McArdle, Wendy L., McGinnis, Ralph, Meyre, David, Munroe, Patricia B., Morris, Andrew D., Ness, Andrew R., Neville, Matthew J., Nica, A.lexandra C., Ong, Ken K., O'Rahilly, Stephen, Owen, Katharine R., Palmer, Colin N., Papadakis, Konstantinos, Potter, Simon, Pouta, Anneli, Qi, Lu, Randall, Joshua C., Rayner, Nigel W., Ring, Susan M., Sandhu, Manjinder S., Scherag, Andre, Sims, Mathew A., Song, Kijoung, Soranzo, Nicole, Speliotes, Elizabeth K., Syddall, Holly E., Teichmann, Sarah A., Timpson, Nicholas J., Tobias, Jonathan H., Uda, Manuela, Ganz Vogel, Carla I., Wallace, Chris, Waterworth, Dawn M., Weedon, Michael N., Willer, Cristen J., Wraight, Vicki L, Zeggini, Eleftheria, Hirschhorn, Joel N., Strachan, David P., Caulfield, Mark J., Samani, Nilesh J., Frayling, Timothy M., Vollenweider, Peter, Waeber, Gerard, Mooser, Vincent, Deloukas, Panos, McCarthy, Mark I., Wareham, Nicholas J., Barroso, Ines, Kraft, Peter, Hankinson, Susan E., Hunter, David J., Hu, Frank B., Lyon, Helen N., Voight, Benjamin F., Ridderstrale, Midderstrale, Groop, Leif, Scheet, Paul, Sanna, Serena, Abecasis, Goncalo R., Albai, Giuseppe, Nagaraja, Ramaiah, Schlessinger, David, Jackson, Anne U., Tuomilehto, Jaakko, Collins, Francis S., Boehnke, Michael, Mohlke, Karen L, Hebebrand, Johannes, Yuan, Xin and Ouwehand, Willem H. (2008) Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nature Genetics, 40 (6), 768-775. (doi:10.1038/ng.140).

Record type: Article

Abstract

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits

This record has no associated files available for download.

More information

Published date: May 2008

Identifiers

Local EPrints ID: 61340
URI: http://eprints.soton.ac.uk/id/eprint/61340
ISSN: 1061-4036
PURE UUID: 3b621549-edd0-4b3a-b979-1a382ba30a34
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for Holly E. Syddall: ORCID iD orcid.org/0000-0003-0171-0306

Catalogue record

Date deposited: 25 Mar 2009
Last modified: 23 Jul 2022 01:43

Export record

Altmetrics

Contributors

Author: Ruth J.F. Loos
Author: Cecilia M. Lindgren
Author: Shengxu Li
Author: Eleanor Wheeler
Author: Jing Hua Zhao
Author: Inga Prokopenko
Author: Michael Inouye
Author: Rachel M. Freathy
Author: Antony P. Attwood
Author: Jacques S. Beckmann
Author: Sonja I. Berndt
Author: Kevin B. Jacobs
Author: Stephen J. Chanock
Author: Richard B. Hayes
Author: Sven Bergmann
Author: Amanda J. Bennett
Author: Sheila A. Bingham
Author: Murielle Bochud
Author: Morris Brown
Author: Stephane Cauchi
Author: John M. Connell
Author: Cyrus Cooper ORCID iD
Author: George Davey Smith
Author: Ian Day
Author: Christian Dina
Author: Subhayoti De
Author: Emmanouil T. Dermitzakis
Author: Alex S.F. Doney
Author: Katherine S. Elliott
Author: Paul Elliott
Author: David M. Evans
Author: I.Sadaf Farooqi
Author: Phillipe Froguel
Author: Jilur Ghori
Author: Christopher J. Groves
Author: Rhian Gwilliam
Author: David Hadley
Author: Alistair S. Hall
Author: A. T. J. Hattersley
Author: Iris M. Heid
Author: Claudia Lamina
Author: Christian Gieger
Author: Thomas Illig
Author: Thomas Meitinger
Author: H-Erich Wichmann
Author: Blanca Herrera
Author: Anke Hinney
Author: Sarah E. Hunt
Author: Manjo-Riitta Jarvelin
Author: Toby Johnson
Author: Jennifer D.M. Jolley
Author: Fredrik Karpe
Author: Andrew Keniry
Author: Kay-Tee Khaw
Author: Robert N. Luben
Author: Massimo Mangino
Author: Jonathan Marchini
Author: Wendy L. McArdle
Author: Ralph McGinnis
Author: David Meyre
Author: Patricia B. Munroe
Author: Andrew D. Morris
Author: Andrew R. Ness
Author: Matthew J. Neville
Author: A.lexandra C. Nica
Author: Ken K. Ong
Author: Stephen O'Rahilly
Author: Katharine R. Owen
Author: Colin N. Palmer
Author: Konstantinos Papadakis
Author: Simon Potter
Author: Anneli Pouta
Author: Lu Qi
Author: Joshua C. Randall
Author: Nigel W. Rayner
Author: Susan M. Ring
Author: Manjinder S. Sandhu
Author: Andre Scherag
Author: Mathew A. Sims
Author: Kijoung Song
Author: Nicole Soranzo
Author: Elizabeth K. Speliotes
Author: Sarah A. Teichmann
Author: Nicholas J. Timpson
Author: Jonathan H. Tobias
Author: Manuela Uda
Author: Carla I. Ganz Vogel
Author: Chris Wallace
Author: Dawn M. Waterworth
Author: Michael N. Weedon
Author: Cristen J. Willer
Author: Vicki L Wraight
Author: Eleftheria Zeggini
Author: Joel N. Hirschhorn
Author: David P. Strachan
Author: Mark J. Caulfield
Author: Nilesh J. Samani
Author: Timothy M. Frayling
Author: Peter Vollenweider
Author: Gerard Waeber
Author: Vincent Mooser
Author: Panos Deloukas
Author: Mark I. McCarthy
Author: Nicholas J. Wareham
Author: Ines Barroso
Author: Peter Kraft
Author: Susan E. Hankinson
Author: David J. Hunter
Author: Frank B. Hu
Author: Helen N. Lyon
Author: Benjamin F. Voight
Author: Midderstrale Ridderstrale
Author: Leif Groop
Author: Paul Scheet
Author: Serena Sanna
Author: Goncalo R. Abecasis
Author: Giuseppe Albai
Author: Ramaiah Nagaraja
Author: David Schlessinger
Author: Anne U. Jackson
Author: Jaakko Tuomilehto
Author: Francis S. Collins
Author: Michael Boehnke
Author: Karen L Mohlke
Author: Johannes Hebebrand
Author: Xin Yuan
Author: Willem H. Ouwehand

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×