Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent

Smith, Caren E.; Follis, Jack L.; Dashti, Hassan S.; Tanaka, Toshiko; Graff, Mariaelisa; Fretts, Amanda M.; Kilpelainen, Tuomas O.; Wojczynski, Mary K.; Richardson, Kris; Nalls, Mike A.; Schulz, Christina-Alexandra; Liu, Yongmei; Frazier-Wood, Alexis C.; van Eekelen, Esther; Wang, Carol; de Vries, Paul S.; Mikkila, Vera; Rohde, Rebecca; Psaty, Bruce M.; Hansen, Torben; Feitosa, Mary F.; Lai, Chao-Qiang; Houston, Denise K.; Ferruci, Luigi; Ericson, Ulrika; Wang, Zhe; de Mutsert, Renee; Oddy, Wendy H.; de Jonge, Ester A. L.; Seppälä, Ilkka; Justice, Anne E.; Lemaitre, Rozenn N.; Sorensen, Thorkild I. A.; Province, Michael A.; Parnell, Laurence D.; Garcia, Melissa E.; Bandinelli, Stefania; Orho-Melander, Marju; Rich, Stephen S.; Rosendaal, Frits R.; Pennell, Craig E.; Kiefte-de Jong, Jessica C.; Kahonen, Mika; Young, Kristin L.; Pedersen, Oluf; Aslibekyan, Stella; Rotter, Jerome I.; Mook-Kanamori, Dennis O.; Zillikens, M. Carola; Raitakari, Olli T.; North, Kari E.; Overvad, Kim; Arnett, Donna K.; Hofman, Albert; Lehtimaki, Terho; Tjonneland, Anne; Uitterlinden, Andre G.; Rivadeneira, Fernando; Franco, Oscar H.; German, J. Bruce; Siscovick, David S.; Cupples, L. Adrienne; & Ordovas, Jose M. (Forthcoming). Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent. Molecular Nutrition & Food Research.

Smith, Caren E.; Follis, Jack L.; Dashti, Hassan S.; Tanaka, Toshiko; Graff, Mariaelisa; Fretts, Amanda M.; Kilpelainen, Tuomas O.; Wojczynski, Mary K.; Richardson, Kris; Nalls, Mike A.; Schulz, Christina-Alexandra; Liu, Yongmei; Frazier-Wood, Alexis C.; van Eekelen, Esther; Wang, Carol; de Vries, Paul S.; Mikkila, Vera; Rohde, Rebecca; Psaty, Bruce M.; Hansen, Torben; Feitosa, Mary F.; Lai, Chao-Qiang; Houston, Denise K.; Ferruci, Luigi; Ericson, Ulrika; Wang, Zhe; de Mutsert, Renee; Oddy, Wendy H.; de Jonge, Ester A. L.; Seppälä, Ilkka; Justice, Anne E.; Lemaitre, Rozenn N.; Sorensen, Thorkild I. A.; Province, Michael A.; Parnell, Laurence D.; Garcia, Melissa E.; Bandinelli, Stefania; Orho-Melander, Marju; Rich, Stephen S.; Rosendaal, Frits R.; Pennell, Craig E.; Kiefte-de Jong, Jessica C.; Kahonen, Mika; Young, Kristin L.; Pedersen, Oluf; Aslibekyan, Stella; Rotter, Jerome I.; Mook-Kanamori, Dennis O.; Zillikens, M. Carola; Raitakari, Olli T.; North, Kari E.; Overvad, Kim; Arnett, Donna K.; Hofman, Albert; Lehtimaki, Terho; Tjonneland, Anne; Uitterlinden, Andre G.; Rivadeneira, Fernando; Franco, Oscar H.; German, J. Bruce; Siscovick, David S.; Cupples, L. Adrienne; & Ordovas, Jose M. (Forthcoming). Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent. Molecular Nutrition & Food Research.

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SCOPE: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption. METHODS AND RESULTS: We conducted a genome-wide interaction study to discover genetic variants that account for variation in BMI in the context of low-fat, high-fat and total dairy intake in cross-sectional analysis. Data from 9 discovery studies (up to 25,513 European descent individuals) were meta-analyzed. Twenty-six genetic variants reached the selected significance threshold (P-interaction <10-7) , and six independent variants (LINC01512-rs7751666, PALM2/AKAP2-rs914359, ACTA2-rs1388, PPP1R12A-rs7961195, LINC00333-rs9635058, AC098847.1-rs1791355) were evaluated meta-analytically for replication of interaction in up to 17,675 individuals. Variant rs9635058 (128 kb 3' of LINC00333) was replicated (P-interaction = 0.004). In the discovery cohorts, rs9635058 interacted with dairy (P-interaction = 7.36 x 10-8) such that each serving of low-fat dairy was associated with 0.225 kg/m2 lower BMI per each additional copy of the effect allele (A). A second genetic variant (ACTA2-rs1388) approached interaction replication significance for low-fat dairy exposure. CONCLUSIONS: Body weight responses to dairy intake may be modified by genotype, in that greater dairy intake may protect a genetic subgroup from higher body weight.




JOUR



Smith, Caren E.
Follis, Jack L.
Dashti, Hassan S.
Tanaka, Toshiko
Graff, Mariaelisa
Fretts, Amanda M.
Kilpelainen, Tuomas O.
Wojczynski, Mary K.
Richardson, Kris
Nalls, Mike A.
Schulz, Christina-Alexandra
Liu, Yongmei
Frazier-Wood, Alexis C.
van Eekelen, Esther
Wang, Carol
de Vries, Paul S.
Mikkila, Vera
Rohde, Rebecca
Psaty, Bruce M.
Hansen, Torben
Feitosa, Mary F.
Lai, Chao-Qiang
Houston, Denise K.
Ferruci, Luigi
Ericson, Ulrika
Wang, Zhe
de Mutsert, Renee
Oddy, Wendy H.
de Jonge, Ester A. L.
Seppälä, Ilkka
Justice, Anne E.
Lemaitre, Rozenn N.
Sorensen, Thorkild I. A.
Province, Michael A.
Parnell, Laurence D.
Garcia, Melissa E.
Bandinelli, Stefania
Orho-Melander, Marju
Rich, Stephen S.
Rosendaal, Frits R.
Pennell, Craig E.
Kiefte-de Jong, Jessica C.
Kahonen, Mika
Young, Kristin L.
Pedersen, Oluf
Aslibekyan, Stella
Rotter, Jerome I.
Mook-Kanamori, Dennis O.
Zillikens, M. Carola
Raitakari, Olli T.
North, Kari E.
Overvad, Kim
Arnett, Donna K.
Hofman, Albert
Lehtimaki, Terho
Tjonneland, Anne
Uitterlinden, Andre G.
Rivadeneira, Fernando
Franco, Oscar H.
German, J. Bruce
Siscovick, David S.
Cupples, L. Adrienne
Ordovas, Jose M.



Forthcoming


Molecular Nutrition & Food Research













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