Abstract
Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04-1×10-17). Except for total HDL particles (r = -0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial {pipe}r{pipe} = 0.07-0.17, P = 5×10-5-1×10-19). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE±0.22 mg/dl/allele, P = 8×10-5, Pinteraction = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE±0.22 mg/dl/allele, P = 0.35) or metformin (β = -0.03, SEE±0.22 mg/dl/allele, P = 0.90; Pinteraction = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE±0.012 ln nmol/L/allele, P = 0.01, Pinteraction = 0.01) but not in the placebo (β = -0.002, SEE±0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE±0.008 nmol/L/allele, P = 0.12; Pinteraction = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss.
| Original language | English (US) |
|---|---|
| Article number | e1002895 |
| Journal | PLoS Genetics |
| Volume | 8 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 2012 |
| Externally published | Yes |
ASJC Scopus subject areas
- Ecology, Evolution, Behavior and Systematics
- Molecular Biology
- Genetics
- Genetics(clinical)
- Cancer Research
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Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment : The Diabetes Prevention Program. / Pollin, Toni I.; Isakova, Tamara; Jablonski, Kathleen A.; de Bakker, Paul I.W.; Taylor, Andrew; McAteer, Jarred; Pan, Qing; Horton, Edward S.; Delahanty, Linda M.; Altshuler, David; Shuldiner, Alan R.; Goldberg, Ronald B.; Florez, Jose C.; Franks, Paul W.; Bray, George A.; Culbert, Iris W.; Champagne, Catherine M.; Eberhardt, Barbara; Greenway, Frank; Guillory, Fonda G.; Herbert, April A.; Jeffirs, Michael L.; Kennedy, Betty M.; Lovejoy, Jennifer C.; Morris, Laura H.; Melancon, Lee E.; Ryan, Donna; Sanford, Deborah A.; Smith, Kenneth G.; Smith, Lisa L.; St. Amant, Julia A.; Tulley, Richard T.; Vicknair, Paula C.; Williamson, Donald; Zachwieja, Jeffery J.; Polonsky, Kenneth S.; Tobian, Janet; Ehrmann, David; Matulik, Margaret J.; Clark, Bart; Czech, Kirsten; DeSandre, Catherine; Hilbrich, Ruthanne; McNabb, Wylie; Semenske, Ann R.; Caro, Jose F.; Watson, Pamela G.; Goldstein, Barry J.; Smith, Kellie A.; Mendoza, Jewel; Liberoni, Renee; Pepe, Constance; Spandorfer, John; Donahue, Richard P.; Goldberg, Ronald B.; Prineas, Ronald; Rowe, Patricia; Calles, Jeanette; Cassanova-Romero, Paul; Florez, Hermes J.; Giannella, Anna; Kirby, Lascelles; Larreal, Carmen; McLymont, Valerie; Mendez, Jadell; Ojito, Juliet; Perry, Arlette; Saab, Patrice; Haffner, Steven M.; Montez, Maria G.; Lorenzo, Carlos; Martinez, Arlene; Hamman, Richard F.; Nash, Patricia V.; Testaverde, Lisa; Anderson, Denise R.; Ballonoff, Larry B.; Bouffard, Alexis; Calonge, B. Ned; Delve, Lynne; Farago, Martha; Hill, James O.; Hoyer, Shelley R.; Jortberg, Bonnie T.; Lenz, Dione; Miller, Marsha; Price, David W.; Regensteiner, Judith G.; Seagle, Helen; Smith, Carissa M.; Steinke, Sheila C.; VanDorsten, Brent; Horton, Edward S.; Lawton, Kathleen E.; Arky, Ronald A.; Bryant, Marybeth; Burke, Jacqueline P.; Caballero, Enrique; Callaphan, Karen M.; Ganda, Om P.; Franklin, Therese; Jackson, Sharon D.; Jacobsen, Alan M.; Jacobsen, Alan M.; Kula, Lyn M.; Kocal, Margaret; Malloy, Maureen A.; Nicosia, Maryanne; Oldmixon, Cathryn F.; Pan, Jocelyn; Quitingon, Marizel; Rubtchinsky, Stacy; Seely, Ellen W.; Schweizer, Dana; Simonson, Donald; Smith, Fannie; Solomon, Caren G.; Warram, James; Kahn, Steven E.; Montgomery, Brenda K.; Fujimoto, Wilfred; Knopp, Robert H.; Lipkin, Edward W.; Marr, Michelle; Trence, Dace; Kitabchi, Abbas E.; Murphy, Mary E.; Applegate, William B.; Bryer-Ash, Michael; Frieson, Sandra L.; Imseis, Raed; Lambeth, Helen; Lichtermann, Lynne C.; Oktaei, Hooman; Rutledge, Lily M.K.; Sherman, Amy R.; Smith, Clara M.; Soberman, Judith E.; Williams-Cleaves, Beverly; Metzger, Boyd E.; Johnson, Mariana K.; Behrends, Catherine; Cook, Michelle; Fitzgibbon, Marian; Giles, Mimi M.; Heard, Deloris; Johnson, Cheryl K.H.; Larsen, Diane; Lowe, Anne; Lyman, Megan; McPherson, David; Molitch, Mark E.; Pitts, Thomas; Reinhart, Renee; Roston, Susan; Schinleber, Pamela A.; Nathan, David M.; McKitrick, Charles; Turgeon, Heather; Abbott, Kathy; Anderson, Ellen; Bissett, Laurie; Cagliero, Enrico; Florez, Jose C.; Delahanty, Linda; Goldman, Valerie; Poulos, Alexandra; Olefsky, Jerrold M.; Carrion-Petersen, Mary Lou; Barrett-Connor, Elizabeth; Edelman, Steven V.; Henry, Robert R.; Horne, Javiva; Janesch, Simona Szerdi; Leos, Diana; Mudaliar, Sundar; Polonsky, William; Smith, Jean; Vejvoda, Karen; Pi-Sunyer, F. Xavier; Lee, Jane E.; Allison, David B.; Aronoff, Nancy J.; Crandall, Jill P.; Foo, Sandra T.; Pal, Carmen; Parkes, Kathy; Pena, Mary Beth; Rooney, Ellen S.; van Wye, Gretchen E.H.; Viscovich, Kristine A.; Marrero, David G.; Prince, Melvin J.; Kelly, Susie M.; Dotson, Yolanda F.; Fineberg, Edwin S.; Guare, John C.; Hadden, Angela M.; Ignaut, James M.; Jackson, Marcia L.; Kirkman, Marion S.; Mather, Kieren J.; Porter, Beverly D.; Roach, Paris J.; Rowland, Nancy D.; Wheeler, Madelyn L.; Ratner, Robert E.; Youssef, Gretchen; Shapiro, Sue; Bavido-Arrage, Catherine; Boggs, Geraldine; Bronsord, Marjorie; Brown, Ernestine; Cheatham, Wayman W.; Cola, Susan; Evans, Cindy; Gibbs, Peggy; Kellum, Tracy; Levatan, Claresa; Nair, Asha K.; Passaro, Maureen; Uwaifo, Gabriel; Saad, Mohammed F.; Budget, Maria; Jinagouda, Sujata; Akbar, Khan; Conzues, Claudia; Magpuri, Perpetua; Ngo, Kathy; Rassam, Amer; Waters, Debra; Xapthalamous, Kathy; Santiago, Julio V.; Dagogo-Jack, Samuel; White, Neil H.; Das, Samia; Santiago, Ana; Brown, Angela; Fisher, Edwin; Hurt, Emma; Jones, Tracy; Kerr, Michelle; Ryder, Lucy; Wernimont, Cormarie; Saudek, Christopher D.; Bradley, Vanessa; Sullivan, Emily; Whittington, Tracy; Abbas, Caroline; Brancati, Frederick L.; Clark, Jeanne M.; Charleston, Jeanne B.; Freel, Janice; Horak, Katherine; Jiggetts, Dawn; Johnson, Deloris; Joseph, Hope; Loman, Kimberly; Mosley, Henry; Rubin, Richard R.; Samuels, Alafia; Stewart, Kerry J.; Williamson, Paula; Schade, David S.; Adams, Karwyn S.; Johannes, Carolyn; Atler, Leslie F.; Boyle, Patrick J.; Burge, Mark R.; Canady, Janene L.; Chai, Lisa; Gonzales, Ysela; Hernandez-McGinnis, Doris A.; Katz, Patricia; King, Carolyn; Rassam, Amer; Rubinchik, Sofya; Senter, Willette; Waters, Debra; Shamoon, Harry; Brown, Janet O.; Adorno, Elsie; Cox, Liane; Crandall, Jill; Duffy, Helena; Engel, Samuel; Friedler, Allison; Howard-Century, Crystal J.; Kloiber, Stacey; Longchamp, Nadege; Martinez, Helen; Pompi, Dorothy; Scheindlin, Jonathan; Violino, Elissa; Walker, Elizabeth; Wylie-Rosett, Judith; Zimmerman, Elise; Zonszein, Joel; Orchard, Trevor; Wing, Rena R.; Koenning, Gaye; Kramer, M. Kaye; Barr, Susan; Boraz, Miriam; Clifford, Lisa; Culyba, Rebecca; Frazier, Marlene; Gilligan, Ryan; Harrier, Susan; Harris, Louann; Jeffries, Susan; Kriska, Andrea; Manjoo, Qurashia; Mullen, Monica; Noel, Alicia; Otto, Amy; Semler, Linda; Smith, Cheryl F.; Smith, Marie; Venditti, Elizabeth; Weinzierl, Valarie; Williams, Katherine V.; Wilson, Tara; Arakaki, Richard F.; Latimer, Renee W.; Baker-Ladao, Narleen K.; Beddow, Ralph; Dias, Lorna; Inouye, Jillian; Mau, Marjorie K.; Mikami, Kathy; Mohideen, Pharis; Odom, Sharon K.; Perry, Raynette U.; Knowler, William C.; Cooeyate, Norman; Hoskin, Mary A.; Percy, Carol A.; Acton, Kelly J.; Andre, Vickie L.; Barber, Rosalyn; Begay, Shandiin; Bennett, Peter H.; Benson, Mary Beth; Bird, Evelyn C.; Broussard, Brenda A.; Chavez, Marcella; Dacawyma, Tara; Doughty, Matthew S.; Duncan, Roberta; Edgerton, Cyndy; Ghahate, Jacqueline M.; Glass, Justin; Glass, Martia; Gohdes, Dorothy; Grant, Wendy; Hanson, Robert L.; Horse, Ellie; Ingraham, Louise E.; Jackson, Merry; Jay, Priscilla; Kaskalla, Roylen S.; Kessler, David; Kobus, Kathleen M.; Krakoff, Jonathan; Manus, Catherine; Michaels, Sara; Morgan, Tina; Nashboo, Yolanda; Nelson, Julie A.; Poirier, Steven; Polczynski, Evette; Reidy, Mike; Roumain, Jeanine; Rowse, Debra; Sangster, Sandra; Sewenemewa, Janet; Tonemah, Darryl; Wilson, Charlton; Yazzie, Michelle; Bain, Raymond; Fowler, Sarah; Brenneman, Tina; Abebe, Solome; Bamdad, Julie; Callaghan, Jackie; Edelstein, Sharon L.; Gao, Yuping; Grimes, Kristina L.; Grover, Nisha; Haffner, Lori; Jones, Steve; Jones, Tara L.; Katz, Richard; Lachin, John M.; Mucik, Pamela; Orlosky, Robert; Rochon, James; Sapozhnikova, Alla; Sherif, Hanna; Stimpson, Charlotte; Temprosa, Marinella; Walker-Murray, Fredricka; Marcovina, Santica; Strylewicz, Greg; Aldrich, F. Alan; O'Leary, Dan; Stamm, Elizabeth; Rautaharju, Pentti; Prineas, Ronald J.; Alexander, Teresa; Campbell, Charles; Hall, Sharon; Li, Yabing; Mills, Margaret; Pemberton, Nancy; Rautaharju, Farida; Zhang, Zhuming; Mayer-Davis, Elizabeth; Moran, Robert R.; Ganiats, Ted; David, Kristin; Sarkin, Andrew J.; Eastman, R.; Fradkin, Judith; Garfield, Sanford; Gregg, Edward; Zhang, Ping; Herman, William; Florez, Jose C.; Altshuler, David; de Bakker, Paul I.W.; Franks, Paul W.; Hanson, Robert L.; Jablonski, Kathleen; Knowler, William C.; McAteer, Jarred B.; Pollin, Toni I.; Shuldiner, Alan R.
In: PLoS Genetics, Vol. 8, No. 8, e1002895, 08.2012.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment
T2 - The Diabetes Prevention Program
AU - Pollin, Toni I.
AU - Isakova, Tamara
AU - Jablonski, Kathleen A.
AU - de Bakker, Paul I.W.
AU - Taylor, Andrew
AU - McAteer, Jarred
AU - Pan, Qing
AU - Horton, Edward S.
AU - Delahanty, Linda M.
AU - Altshuler, David
AU - Shuldiner, Alan R.
AU - Goldberg, Ronald B.
AU - Florez, Jose C.
AU - Franks, Paul W.
AU - Bray, George A.
AU - Culbert, Iris W.
AU - Champagne, Catherine M.
AU - Eberhardt, Barbara
AU - Greenway, Frank
AU - Guillory, Fonda G.
AU - Herbert, April A.
AU - Jeffirs, Michael L.
AU - Kennedy, Betty M.
AU - Lovejoy, Jennifer C.
AU - Morris, Laura H.
AU - Melancon, Lee E.
AU - Ryan, Donna
AU - Sanford, Deborah A.
AU - Smith, Kenneth G.
AU - Smith, Lisa L.
AU - St. Amant, Julia A.
AU - Tulley, Richard T.
AU - Vicknair, Paula C.
AU - Williamson, Donald
AU - Zachwieja, Jeffery J.
AU - Polonsky, Kenneth S.
AU - Tobian, Janet
AU - Ehrmann, David
AU - Matulik, Margaret J.
AU - Clark, Bart
AU - Czech, Kirsten
AU - DeSandre, Catherine
AU - Hilbrich, Ruthanne
AU - McNabb, Wylie
AU - Semenske, Ann R.
AU - Caro, Jose F.
AU - Watson, Pamela G.
AU - Goldstein, Barry J.
AU - Smith, Kellie A.
AU - Mendoza, Jewel
AU - Liberoni, Renee
AU - Pepe, Constance
AU - Spandorfer, John
AU - Donahue, Richard P.
AU - Goldberg, Ronald B.
AU - Prineas, Ronald
AU - Rowe, Patricia
AU - Calles, Jeanette
AU - Cassanova-Romero, Paul
AU - Florez, Hermes J.
AU - Giannella, Anna
AU - Kirby, Lascelles
AU - Larreal, Carmen
AU - McLymont, Valerie
AU - Mendez, Jadell
AU - Ojito, Juliet
AU - Perry, Arlette
AU - Saab, Patrice
AU - Haffner, Steven M.
AU - Montez, Maria G.
AU - Lorenzo, Carlos
AU - Martinez, Arlene
AU - Hamman, Richard F.
AU - Nash, Patricia V.
AU - Testaverde, Lisa
AU - Anderson, Denise R.
AU - Ballonoff, Larry B.
AU - Bouffard, Alexis
AU - Calonge, B. Ned
AU - Delve, Lynne
AU - Farago, Martha
AU - Hill, James O.
AU - Hoyer, Shelley R.
AU - Jortberg, Bonnie T.
AU - Lenz, Dione
AU - Miller, Marsha
AU - Price, David W.
AU - Regensteiner, Judith G.
AU - Seagle, Helen
AU - Smith, Carissa M.
AU - Steinke, Sheila C.
AU - VanDorsten, Brent
AU - Horton, Edward S.
AU - Lawton, Kathleen E.
AU - Arky, Ronald A.
AU - Bryant, Marybeth
AU - Burke, Jacqueline P.
AU - Caballero, Enrique
AU - Callaphan, Karen M.
AU - Ganda, Om P.
AU - Franklin, Therese
AU - Jackson, Sharon D.
AU - Jacobsen, Alan M.
AU - Jacobsen, Alan M.
AU - Kula, Lyn M.
AU - Kocal, Margaret
AU - Malloy, Maureen A.
AU - Nicosia, Maryanne
AU - Oldmixon, Cathryn F.
AU - Pan, Jocelyn
AU - Quitingon, Marizel
AU - Rubtchinsky, Stacy
AU - Seely, Ellen W.
AU - Schweizer, Dana
AU - Simonson, Donald
AU - Smith, Fannie
AU - Solomon, Caren G.
AU - Warram, James
AU - Kahn, Steven E.
AU - Montgomery, Brenda K.
AU - Fujimoto, Wilfred
AU - Knopp, Robert H.
AU - Lipkin, Edward W.
AU - Marr, Michelle
AU - Trence, Dace
AU - Kitabchi, Abbas E.
AU - Murphy, Mary E.
AU - Applegate, William B.
AU - Bryer-Ash, Michael
AU - Frieson, Sandra L.
AU - Imseis, Raed
AU - Lambeth, Helen
AU - Lichtermann, Lynne C.
AU - Oktaei, Hooman
AU - Rutledge, Lily M.K.
AU - Sherman, Amy R.
AU - Smith, Clara M.
AU - Soberman, Judith E.
AU - Williams-Cleaves, Beverly
AU - Metzger, Boyd E.
AU - Johnson, Mariana K.
AU - Behrends, Catherine
AU - Cook, Michelle
AU - Fitzgibbon, Marian
AU - Giles, Mimi M.
AU - Heard, Deloris
AU - Johnson, Cheryl K.H.
AU - Larsen, Diane
AU - Lowe, Anne
AU - Lyman, Megan
AU - McPherson, David
AU - Molitch, Mark E.
AU - Pitts, Thomas
AU - Reinhart, Renee
AU - Roston, Susan
AU - Schinleber, Pamela A.
AU - Nathan, David M.
AU - McKitrick, Charles
AU - Turgeon, Heather
AU - Abbott, Kathy
AU - Anderson, Ellen
AU - Bissett, Laurie
AU - Cagliero, Enrico
AU - Florez, Jose C.
AU - Delahanty, Linda
AU - Goldman, Valerie
AU - Poulos, Alexandra
AU - Olefsky, Jerrold M.
AU - Carrion-Petersen, Mary Lou
AU - Barrett-Connor, Elizabeth
AU - Edelman, Steven V.
AU - Henry, Robert R.
AU - Horne, Javiva
AU - Janesch, Simona Szerdi
AU - Leos, Diana
AU - Mudaliar, Sundar
AU - Polonsky, William
AU - Smith, Jean
AU - Vejvoda, Karen
AU - Pi-Sunyer, F. Xavier
AU - Lee, Jane E.
AU - Allison, David B.
AU - Aronoff, Nancy J.
AU - Crandall, Jill P.
AU - Foo, Sandra T.
AU - Pal, Carmen
AU - Parkes, Kathy
AU - Pena, Mary Beth
AU - Rooney, Ellen S.
AU - van Wye, Gretchen E.H.
AU - Viscovich, Kristine A.
AU - Marrero, David G.
AU - Prince, Melvin J.
AU - Kelly, Susie M.
AU - Dotson, Yolanda F.
AU - Fineberg, Edwin S.
AU - Guare, John C.
AU - Hadden, Angela M.
AU - Ignaut, James M.
AU - Jackson, Marcia L.
AU - Kirkman, Marion S.
AU - Mather, Kieren J.
AU - Porter, Beverly D.
AU - Roach, Paris J.
AU - Rowland, Nancy D.
AU - Wheeler, Madelyn L.
AU - Ratner, Robert E.
AU - Youssef, Gretchen
AU - Shapiro, Sue
AU - Bavido-Arrage, Catherine
AU - Boggs, Geraldine
AU - Bronsord, Marjorie
AU - Brown, Ernestine
AU - Cheatham, Wayman W.
AU - Cola, Susan
AU - Evans, Cindy
AU - Gibbs, Peggy
AU - Kellum, Tracy
AU - Levatan, Claresa
AU - Nair, Asha K.
AU - Passaro, Maureen
AU - Uwaifo, Gabriel
AU - Saad, Mohammed F.
AU - Budget, Maria
AU - Jinagouda, Sujata
AU - Akbar, Khan
AU - Conzues, Claudia
AU - Magpuri, Perpetua
AU - Ngo, Kathy
AU - Rassam, Amer
AU - Waters, Debra
AU - Xapthalamous, Kathy
AU - Santiago, Julio V.
AU - Dagogo-Jack, Samuel
AU - White, Neil H.
AU - Das, Samia
AU - Santiago, Ana
AU - Brown, Angela
AU - Fisher, Edwin
AU - Hurt, Emma
AU - Jones, Tracy
AU - Kerr, Michelle
AU - Ryder, Lucy
AU - Wernimont, Cormarie
AU - Saudek, Christopher D.
AU - Bradley, Vanessa
AU - Sullivan, Emily
AU - Whittington, Tracy
AU - Abbas, Caroline
AU - Brancati, Frederick L.
AU - Clark, Jeanne M.
AU - Charleston, Jeanne B.
AU - Freel, Janice
AU - Horak, Katherine
AU - Jiggetts, Dawn
AU - Johnson, Deloris
AU - Joseph, Hope
AU - Loman, Kimberly
AU - Mosley, Henry
AU - Rubin, Richard R.
AU - Samuels, Alafia
AU - Stewart, Kerry J.
AU - Williamson, Paula
AU - Schade, David S.
AU - Adams, Karwyn S.
AU - Johannes, Carolyn
AU - Atler, Leslie F.
AU - Boyle, Patrick J.
AU - Burge, Mark R.
AU - Canady, Janene L.
AU - Chai, Lisa
AU - Gonzales, Ysela
AU - Hernandez-McGinnis, Doris A.
AU - Katz, Patricia
AU - King, Carolyn
AU - Rassam, Amer
AU - Rubinchik, Sofya
AU - Senter, Willette
AU - Waters, Debra
AU - Shamoon, Harry
AU - Brown, Janet O.
AU - Adorno, Elsie
AU - Cox, Liane
AU - Crandall, Jill
AU - Duffy, Helena
AU - Engel, Samuel
AU - Friedler, Allison
AU - Howard-Century, Crystal J.
AU - Kloiber, Stacey
AU - Longchamp, Nadege
AU - Martinez, Helen
AU - Pompi, Dorothy
AU - Scheindlin, Jonathan
AU - Violino, Elissa
AU - Walker, Elizabeth
AU - Wylie-Rosett, Judith
AU - Zimmerman, Elise
AU - Zonszein, Joel
AU - Orchard, Trevor
AU - Wing, Rena R.
AU - Koenning, Gaye
AU - Kramer, M. Kaye
AU - Barr, Susan
AU - Boraz, Miriam
AU - Clifford, Lisa
AU - Culyba, Rebecca
AU - Frazier, Marlene
AU - Gilligan, Ryan
AU - Harrier, Susan
AU - Harris, Louann
AU - Jeffries, Susan
AU - Kriska, Andrea
AU - Manjoo, Qurashia
AU - Mullen, Monica
AU - Noel, Alicia
AU - Otto, Amy
AU - Semler, Linda
AU - Smith, Cheryl F.
AU - Smith, Marie
AU - Venditti, Elizabeth
AU - Weinzierl, Valarie
AU - Williams, Katherine V.
AU - Wilson, Tara
AU - Arakaki, Richard F.
AU - Latimer, Renee W.
AU - Baker-Ladao, Narleen K.
AU - Beddow, Ralph
AU - Dias, Lorna
AU - Inouye, Jillian
AU - Mau, Marjorie K.
AU - Mikami, Kathy
AU - Mohideen, Pharis
AU - Odom, Sharon K.
AU - Perry, Raynette U.
AU - Knowler, William C.
AU - Cooeyate, Norman
AU - Hoskin, Mary A.
AU - Percy, Carol A.
AU - Acton, Kelly J.
AU - Andre, Vickie L.
AU - Barber, Rosalyn
AU - Begay, Shandiin
AU - Bennett, Peter H.
AU - Benson, Mary Beth
AU - Bird, Evelyn C.
AU - Broussard, Brenda A.
AU - Chavez, Marcella
AU - Dacawyma, Tara
AU - Doughty, Matthew S.
AU - Duncan, Roberta
AU - Edgerton, Cyndy
AU - Ghahate, Jacqueline M.
AU - Glass, Justin
AU - Glass, Martia
AU - Gohdes, Dorothy
AU - Grant, Wendy
AU - Hanson, Robert L.
AU - Horse, Ellie
AU - Ingraham, Louise E.
AU - Jackson, Merry
AU - Jay, Priscilla
AU - Kaskalla, Roylen S.
AU - Kessler, David
AU - Kobus, Kathleen M.
AU - Krakoff, Jonathan
AU - Manus, Catherine
AU - Michaels, Sara
AU - Morgan, Tina
AU - Nashboo, Yolanda
AU - Nelson, Julie A.
AU - Poirier, Steven
AU - Polczynski, Evette
AU - Reidy, Mike
AU - Roumain, Jeanine
AU - Rowse, Debra
AU - Sangster, Sandra
AU - Sewenemewa, Janet
AU - Tonemah, Darryl
AU - Wilson, Charlton
AU - Yazzie, Michelle
AU - Bain, Raymond
AU - Fowler, Sarah
AU - Brenneman, Tina
AU - Abebe, Solome
AU - Bamdad, Julie
AU - Callaghan, Jackie
AU - Edelstein, Sharon L.
AU - Gao, Yuping
AU - Grimes, Kristina L.
AU - Grover, Nisha
AU - Haffner, Lori
AU - Jones, Steve
AU - Jones, Tara L.
AU - Katz, Richard
AU - Lachin, John M.
AU - Mucik, Pamela
AU - Orlosky, Robert
AU - Rochon, James
AU - Sapozhnikova, Alla
AU - Sherif, Hanna
AU - Stimpson, Charlotte
AU - Temprosa, Marinella
AU - Walker-Murray, Fredricka
AU - Marcovina, Santica
AU - Strylewicz, Greg
AU - Aldrich, F. Alan
AU - O'Leary, Dan
AU - Stamm, Elizabeth
AU - Rautaharju, Pentti
AU - Prineas, Ronald J.
AU - Alexander, Teresa
AU - Campbell, Charles
AU - Hall, Sharon
AU - Li, Yabing
AU - Mills, Margaret
AU - Pemberton, Nancy
AU - Rautaharju, Farida
AU - Zhang, Zhuming
AU - Mayer-Davis, Elizabeth
AU - Moran, Robert R.
AU - Ganiats, Ted
AU - David, Kristin
AU - Sarkin, Andrew J.
AU - Eastman, R.
AU - Fradkin, Judith
AU - Garfield, Sanford
AU - Gregg, Edward
AU - Zhang, Ping
AU - Herman, William
AU - Florez, Jose C.
AU - Altshuler, David
AU - de Bakker, Paul I.W.
AU - Franks, Paul W.
AU - Hanson, Robert L.
AU - Jablonski, Kathleen
AU - Knowler, William C.
AU - McAteer, Jarred B.
AU - Pollin, Toni I.
AU - Shuldiner, Alan R.
N1 - Funding Information: TIP has been a consultant for Isis Pharmaceuticals. TI has received a research grant from NIDDK and honoraria from Shire and Genzyme and has been a consultant for Shire. KAJ (the DPP Genetics Program) has a research grant from NIH. DA has received a research grant from Pfizer and honoraria from academic non-profit (e.g. talks) and has been a consultant for Eisai, MPM Capital, and NanoString. ARS has a NIH research grant. RBG has a research grant from NIH for this study; speaker honoraria from Merck; other research support from Bristol Myers Squibb, GSK, and Roche; and small consultant activities. JCF has received consulting honoraria from Daiichi-Sankyo and AstraZeneca. PWF has received speaking honoraria from Novo Nordisk and other academic/non-profit organisations.
PY - 2012/8
Y1 - 2012/8
N2 - Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04-1×10-17). Except for total HDL particles (r = -0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial {pipe}r{pipe} = 0.07-0.17, P = 5×10-5-1×10-19). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE±0.22 mg/dl/allele, P = 8×10-5, Pinteraction = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE±0.22 mg/dl/allele, P = 0.35) or metformin (β = -0.03, SEE±0.22 mg/dl/allele, P = 0.90; Pinteraction = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE±0.012 ln nmol/L/allele, P = 0.01, Pinteraction = 0.01) but not in the placebo (β = -0.002, SEE±0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE±0.008 nmol/L/allele, P = 0.12; Pinteraction = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss.
AB - Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04-1×10-17). Except for total HDL particles (r = -0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial {pipe}r{pipe} = 0.07-0.17, P = 5×10-5-1×10-19). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE±0.22 mg/dl/allele, P = 8×10-5, Pinteraction = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE±0.22 mg/dl/allele, P = 0.35) or metformin (β = -0.03, SEE±0.22 mg/dl/allele, P = 0.90; Pinteraction = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE±0.012 ln nmol/L/allele, P = 0.01, Pinteraction = 0.01) but not in the placebo (β = -0.002, SEE±0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE±0.008 nmol/L/allele, P = 0.12; Pinteraction = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss.
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U2 - 10.1371/journal.pgen.1002895
DO - 10.1371/journal.pgen.1002895
M3 - Article
C2 - 22951888
AN - SCOPUS:84866155075
VL - 8
JO - PLoS Genetics
JF - PLoS Genetics
SN - 1553-7390
IS - 8
M1 - e1002895
ER -