Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity

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Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity. / Yaghootkar, Hanieh; Zhang, Yiying; Spracklen, Cassandra N; Karaderi, Tugce; Huang, Lam Opal; Bradfield, Jonathan; Schurmann, Claudia; Fine, Rebecca S; Preuss, Michael H; Kutalik, Zoltan; Wittemans, Laura Bl; Lu, Yingchang; Metz, Sophia; Willems, Sara M; Li-Gao, Ruifang; Grarup, Niels; Wang, Shuai; Molnos, Sophie; Sandoval-Zárate, América A; Nalls, Mike A; Lange, Leslie A; Haesser, Jeffrey; Guo, Xiuqing; Lyytikäinen, Leo-Pekka; Feitosa, Mary F; Sitlani, Colleen M; Venturini, Cristina; Mahajan, Anubha; Kacprowski, Tim; Wang, Carol A; Chasman, Daniel I; Amin, Najaf; Broer, Linda; Robertson, Neil; Young, Kristin L; Allison, Matthew; Auer, Paul L; Blüher, Matthias; Borja, Judith B; Bork-Jensen, Jette; Carrasquilla, Germán D; Christofidou, Paraskevi; Demirkan, Ayse; Doege, Claudia A; Jakupovic, Hermina; Li, Jin; Lind, Lars; Kovacs, Peter; Hansen, Torben; Loos, Ruth JF; Kilpeläinen, Tuomas O; Leptin Exomechip Collaboration.

In: Diabetes, Vol. 69, No. 11, 2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Yaghootkar, H, Zhang, Y, Spracklen, CN, Karaderi, T, Huang, LO, Bradfield, J, Schurmann, C, Fine, RS, Preuss, MH, Kutalik, Z, Wittemans, LB, Lu, Y, Metz, S, Willems, SM, Li-Gao, R, Grarup, N, Wang, S, Molnos, S, Sandoval-Zárate, AA, Nalls, MA, Lange, LA, Haesser, J, Guo, X, Lyytikäinen, L-P, Feitosa, MF, Sitlani, CM, Venturini, C, Mahajan, A, Kacprowski, T, Wang, CA, Chasman, DI, Amin, N, Broer, L, Robertson, N, Young, KL, Allison, M, Auer, PL, Blüher, M, Borja, JB, Bork-Jensen, J, Carrasquilla, GD, Christofidou, P, Demirkan, A, Doege, CA, Jakupovic, H, Li, J, Lind, L, Kovacs, P, Hansen, T, Loos, RJF, Kilpeläinen, TO & Leptin Exomechip Collaboration 2020, 'Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity', Diabetes, vol. 69, no. 11. https://doi.org/10.2337/db20-0070

APA

Yaghootkar, H., Zhang, Y., Spracklen, C. N., Karaderi, T., Huang, L. O., Bradfield, J., Schurmann, C., Fine, R. S., Preuss, M. H., Kutalik, Z., Wittemans, L. B., Lu, Y., Metz, S., Willems, S. M., Li-Gao, R., Grarup, N., Wang, S., Molnos, S., Sandoval-Zárate, A. A., ... Leptin Exomechip Collaboration (2020). Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity. Diabetes, 69(11). https://doi.org/10.2337/db20-0070

Vancouver

Yaghootkar H, Zhang Y, Spracklen CN, Karaderi T, Huang LO, Bradfield J et al. Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity. Diabetes. 2020;69(11). https://doi.org/10.2337/db20-0070

Author

Yaghootkar, Hanieh ; Zhang, Yiying ; Spracklen, Cassandra N ; Karaderi, Tugce ; Huang, Lam Opal ; Bradfield, Jonathan ; Schurmann, Claudia ; Fine, Rebecca S ; Preuss, Michael H ; Kutalik, Zoltan ; Wittemans, Laura Bl ; Lu, Yingchang ; Metz, Sophia ; Willems, Sara M ; Li-Gao, Ruifang ; Grarup, Niels ; Wang, Shuai ; Molnos, Sophie ; Sandoval-Zárate, América A ; Nalls, Mike A ; Lange, Leslie A ; Haesser, Jeffrey ; Guo, Xiuqing ; Lyytikäinen, Leo-Pekka ; Feitosa, Mary F ; Sitlani, Colleen M ; Venturini, Cristina ; Mahajan, Anubha ; Kacprowski, Tim ; Wang, Carol A ; Chasman, Daniel I ; Amin, Najaf ; Broer, Linda ; Robertson, Neil ; Young, Kristin L ; Allison, Matthew ; Auer, Paul L ; Blüher, Matthias ; Borja, Judith B ; Bork-Jensen, Jette ; Carrasquilla, Germán D ; Christofidou, Paraskevi ; Demirkan, Ayse ; Doege, Claudia A ; Jakupovic, Hermina ; Li, Jin ; Lind, Lars ; Kovacs, Peter ; Hansen, Torben ; Loos, Ruth JF ; Kilpeläinen, Tuomas O ; Leptin Exomechip Collaboration. / Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity. In: Diabetes. 2020 ; Vol. 69, No. 11.

Bibtex

@article{2baf251bd39f4ce1a9cf8c46263c295e,
title = "Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity",
abstract = "Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14 The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only and its association with lower leptin concentrations was specific to this ancestry (P=2x10-16, n=3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting leptin regulates early adiposity.",
author = "Hanieh Yaghootkar and Yiying Zhang and Spracklen, {Cassandra N} and Tugce Karaderi and Huang, {Lam Opal} and Jonathan Bradfield and Claudia Schurmann and Fine, {Rebecca S} and Preuss, {Michael H} and Zoltan Kutalik and Wittemans, {Laura Bl} and Yingchang Lu and Sophia Metz and Willems, {Sara M} and Ruifang Li-Gao and Niels Grarup and Shuai Wang and Sophie Molnos and Sandoval-Z{\'a}rate, {Am{\'e}rica A} and Nalls, {Mike A} and Lange, {Leslie A} and Jeffrey Haesser and Xiuqing Guo and Leo-Pekka Lyytik{\"a}inen and Feitosa, {Mary F} and Sitlani, {Colleen M} and Cristina Venturini and Anubha Mahajan and Tim Kacprowski and Wang, {Carol A} and Chasman, {Daniel I} and Najaf Amin and Linda Broer and Neil Robertson and Young, {Kristin L} and Matthew Allison and Auer, {Paul L} and Matthias Bl{\"u}her and Borja, {Judith B} and Jette Bork-Jensen and Carrasquilla, {Germ{\'a}n D} and Paraskevi Christofidou and Ayse Demirkan and Doege, {Claudia A} and Hermina Jakupovic and Jin Li and Lars Lind and Peter Kovacs and Torben Hansen and Loos, {Ruth JF} and Kilpel{\"a}inen, {Tuomas O} and {Leptin Exomechip Collaboration}",
year = "2020",
doi = "10.2337/db20-0070",
language = "English",
volume = "69",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "11",

}

RIS

TY - JOUR

T1 - Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity

AU - Yaghootkar, Hanieh

AU - Zhang, Yiying

AU - Spracklen, Cassandra N

AU - Karaderi, Tugce

AU - Huang, Lam Opal

AU - Bradfield, Jonathan

AU - Schurmann, Claudia

AU - Fine, Rebecca S

AU - Preuss, Michael H

AU - Kutalik, Zoltan

AU - Wittemans, Laura Bl

AU - Lu, Yingchang

AU - Metz, Sophia

AU - Willems, Sara M

AU - Li-Gao, Ruifang

AU - Grarup, Niels

AU - Wang, Shuai

AU - Molnos, Sophie

AU - Sandoval-Zárate, América A

AU - Nalls, Mike A

AU - Lange, Leslie A

AU - Haesser, Jeffrey

AU - Guo, Xiuqing

AU - Lyytikäinen, Leo-Pekka

AU - Feitosa, Mary F

AU - Sitlani, Colleen M

AU - Venturini, Cristina

AU - Mahajan, Anubha

AU - Kacprowski, Tim

AU - Wang, Carol A

AU - Chasman, Daniel I

AU - Amin, Najaf

AU - Broer, Linda

AU - Robertson, Neil

AU - Young, Kristin L

AU - Allison, Matthew

AU - Auer, Paul L

AU - Blüher, Matthias

AU - Borja, Judith B

AU - Bork-Jensen, Jette

AU - Carrasquilla, Germán D

AU - Christofidou, Paraskevi

AU - Demirkan, Ayse

AU - Doege, Claudia A

AU - Jakupovic, Hermina

AU - Li, Jin

AU - Lind, Lars

AU - Kovacs, Peter

AU - Hansen, Torben

AU - Loos, Ruth JF

AU - Kilpeläinen, Tuomas O

AU - Leptin Exomechip Collaboration

PY - 2020

Y1 - 2020

N2 - Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14 The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only and its association with lower leptin concentrations was specific to this ancestry (P=2x10-16, n=3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting leptin regulates early adiposity.

AB - Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14 The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only and its association with lower leptin concentrations was specific to this ancestry (P=2x10-16, n=3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting leptin regulates early adiposity.

U2 - 10.2337/db20-0070

DO - 10.2337/db20-0070

M3 - Journal article

C2 - 32917775

VL - 69

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 11

ER -

ID: 248649629