Impact of Amerind ancestry and FADS genetic variation on omega-3 deficiency and cardiometabolic traits in Hispanic populations

Chaojie Yang; Brian Hallmark; Jin Choul Chai; Timothy D. O’Connor; Lindsay M. Reynolds; Alexis C. Wood; Michael Seeds; Yii Der Ida Chen; Lyn M. Steffen; Michael Y. Tsai; Robert C. Kaplan; Martha L. Daviglus; Lawrence J. Mandarino; Amanda M. Fretts; Rozenn N. Lemaitre; Dawn K. Coletta; Sarah A. Blomquist; Laurel M. Johnstone; Chandra Tontsch; Qibin Qi; Ingo Ruczinski; Stephen S. Rich; Rasika A. Mathias; Floyd H. Chilton; Ani Manichaikul

doi:10.1038/s42003-021-02431-4

Impact of Amerind ancestry and FADS genetic variation on omega-3 deficiency and cardiometabolic traits in Hispanic populations

Chaojie Yang, Brian Hallmark, Jin Choul Chai, Timothy D. O’Connor, Lindsay M. Reynolds, Alexis C. Wood, Michael Seeds, Yii Der Ida Chen, Lyn M. Steffen, Michael Y. Tsai, Robert C. Kaplan, Martha L. Daviglus, Lawrence J. Mandarino, Amanda M. Fretts, Rozenn N. Lemaitre, Dawn K. Coletta, Sarah A. Blomquist, Laurel M. Johnstone, Chandra Tontsch, Qibin QiIngo Ruczinski, Stephen S. Rich, Rasika A. Mathias, Floyd H. Chilton, Ani Manichaikul

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Long chain polyunsaturated fatty acids (LC-PUFAs) have critical signaling roles that regulate dyslipidemia and inflammation. Genetic variation in the FADS gene cluster accounts for a large portion of interindividual differences in circulating and tissue levels of LC-PUFAs, with the genotypes most strongly predictive of low LC-PUFA levels at strikingly higher frequencies in Amerind ancestry populations. In this study, we examined relationships between genetic ancestry and FADS variation in 1102 Hispanic American participants from the Multi-Ethnic Study of Atherosclerosis. We demonstrate strong negative associations between Amerind genetic ancestry and LC-PUFA levels. The FADS rs174537 single nucleotide polymorphism (SNP) accounted for much of the AI ancestry effect on LC-PUFAs, especially for low levels of n-3 LC-PUFAs. Rs174537 was also strongly associated with several metabolic, inflammatory and anthropomorphic traits including circulating triglycerides (TGs) and E-selectin in MESA Hispanics. Our study demonstrates that Amerind ancestry provides a useful and readily available tool to identify individuals most likely to have FADS-related n-3 LC-PUFA deficiencies and associated cardiovascular risk.

Original language	English (US)
Article number	918
Journal	Communications biology
Volume	4
Issue number	1
DOIs	https://doi.org/10.1038/s42003-021-02431-4
State	Published - Dec 2021

Bibliographical note

Funding Information:
This work was supported by NCCIH R01 AT008621 and USDA ARZT-1361680-H23-157. The Multi-Ethnic Study of Atherosclerosis: MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881, and DK063491. Funding for SHARe genotyping was provided by NHLBI Contract N02-HL-64278. Genotyping was performed at Affymetrix (Santa Clara, California, USA) and the Broad Institute of Harvard and MIT (Boston, Massachusetts, USA) using the Affymetrix Genome-Wide Human SNP Array 6.0. The Hispanic Community Health Study/Study of Latinos: HCHS/SOL is a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (HHSN268201300001I/N01-HC-65233), University of Miami (HHSN268201300004I/N01-HC-65234), Albert Einstein College of Medicine (HHSN268201300002I/N01-HC-65235), University of Illinois at Chicago (HHSN268201300003I/N01-HC-65236 Northwestern Univ), and San Diego State University (HHSN268201300005I/N01-HC-65237). The following Institutes/Centers/Offices have contributed to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Neurological Disorders and Stroke, and NIH Institution-Office of Dietary Supplements. The authors thank the staff and participants of HCHS/SOL for their important contributions. A complete list of staff and investigators has been provided by Sorlie P., et al. in Ann. Epidemiol. 2010 Aug;20: 642–649 and is also available on the study website http://www.cscc.unc.edu/hchs/. Other funding sources for this study include R01HL060712, R01HL140976, and R01HL136266 from the NHLBI; and R01DK119268, R01DK120870 and the New York Regional Center for Diabetes Translation Research (P30 DK111022) from the NIDDK. The Genetic Analysis Center at the University of Washington was supported by NHLBI and NIDCR contracts (HHSN268201300005C AM03 and MOD03). Genotyping efforts were supported by NHLBI HSN 26220/20054C, NCATS CTSI grant UL1TR000123, and NIDDK Diabetes Research Center (DRC) grant DK063491. The Arizona Insulin Resistance Registry: The AIR registry was supported by Health Research Alliance Arizona and the Center for Metabolic Biology at Arizona State University. Data management support was provided by a grant (UL1 RR024150) from the Mayo Clinic to utilize Research Electronic Data Capture (REDCap).

Publisher Copyright:
© 2021, The Author(s).

Publisher link

10.1038/s42003-021-02431-4

Find It

Find It at U of M Libraries

Cite this

Yang, C., Hallmark, B., Chai, J. C., O’Connor, T. D., Reynolds, L. M., Wood, A. C., Seeds, M., Chen, Y. D. I., Steffen, L. M., Tsai, M. Y., Kaplan, R. C., Daviglus, M. L., Mandarino, L. J., Fretts, A. M., Lemaitre, R. N., Coletta, D. K., Blomquist, S. A., Johnstone, L. M., Tontsch, C., ... Manichaikul, A. (2021). Impact of Amerind ancestry and FADS genetic variation on omega-3 deficiency and cardiometabolic traits in Hispanic populations. Communications biology, 4(1), Article 918. https://doi.org/10.1038/s42003-021-02431-4

Yang, C, Hallmark, B, Chai, JC, O’Connor, TD, Reynolds, LM, Wood, AC, Seeds, M, Chen, YDI, Steffen, LM , Tsai, MY, Kaplan, RC, Daviglus, ML, Mandarino, LJ, Fretts, AM, Lemaitre, RN, Coletta, DK, Blomquist, SA, Johnstone, LM, Tontsch, C, Qi, Q, Ruczinski, I, Rich, SS, Mathias, RA, Chilton, FH & Manichaikul, A 2021, 'Impact of Amerind ancestry and FADS genetic variation on omega-3 deficiency and cardiometabolic traits in Hispanic populations', Communications biology, vol. 4, no. 1, 918. https://doi.org/10.1038/s42003-021-02431-4

@article{1258cd71825f4df59f28b5e129a02bf5,

title = "Impact of Amerind ancestry and FADS genetic variation on omega-3 deficiency and cardiometabolic traits in Hispanic populations",

abstract = "Long chain polyunsaturated fatty acids (LC-PUFAs) have critical signaling roles that regulate dyslipidemia and inflammation. Genetic variation in the FADS gene cluster accounts for a large portion of interindividual differences in circulating and tissue levels of LC-PUFAs, with the genotypes most strongly predictive of low LC-PUFA levels at strikingly higher frequencies in Amerind ancestry populations. In this study, we examined relationships between genetic ancestry and FADS variation in 1102 Hispanic American participants from the Multi-Ethnic Study of Atherosclerosis. We demonstrate strong negative associations between Amerind genetic ancestry and LC-PUFA levels. The FADS rs174537 single nucleotide polymorphism (SNP) accounted for much of the AI ancestry effect on LC-PUFAs, especially for low levels of n-3 LC-PUFAs. Rs174537 was also strongly associated with several metabolic, inflammatory and anthropomorphic traits including circulating triglycerides (TGs) and E-selectin in MESA Hispanics. Our study demonstrates that Amerind ancestry provides a useful and readily available tool to identify individuals most likely to have FADS-related n-3 LC-PUFA deficiencies and associated cardiovascular risk.",

author = "Chaojie Yang and Brian Hallmark and Chai, {Jin Choul} and O{\textquoteright}Connor, {Timothy D.} and Reynolds, {Lindsay M.} and Wood, {Alexis C.} and Michael Seeds and Chen, {Yii Der Ida} and Steffen, {Lyn M.} and Tsai, {Michael Y.} and Kaplan, {Robert C.} and Daviglus, {Martha L.} and Mandarino, {Lawrence J.} and Fretts, {Amanda M.} and Lemaitre, {Rozenn N.} and Coletta, {Dawn K.} and Blomquist, {Sarah A.} and Johnstone, {Laurel M.} and Chandra Tontsch and Qibin Qi and Ingo Ruczinski and Rich, {Stephen S.} and Mathias, {Rasika A.} and Chilton, {Floyd H.} and Ani Manichaikul",

note = "Funding Information: This work was supported by NCCIH R01 AT008621 and USDA ARZT-1361680-H23-157. The Multi-Ethnic Study of Atherosclerosis: MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881, and DK063491. Funding for SHARe genotyping was provided by NHLBI Contract N02-HL-64278. Genotyping was performed at Affymetrix (Santa Clara, California, USA) and the Broad Institute of Harvard and MIT (Boston, Massachusetts, USA) using the Affymetrix Genome-Wide Human SNP Array 6.0. The Hispanic Community Health Study/Study of Latinos: HCHS/SOL is a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (HHSN268201300001I/N01-HC-65233), University of Miami (HHSN268201300004I/N01-HC-65234), Albert Einstein College of Medicine (HHSN268201300002I/N01-HC-65235), University of Illinois at Chicago (HHSN268201300003I/N01-HC-65236 Northwestern Univ), and San Diego State University (HHSN268201300005I/N01-HC-65237). The following Institutes/Centers/Offices have contributed to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Neurological Disorders and Stroke, and NIH Institution-Office of Dietary Supplements. The authors thank the staff and participants of HCHS/SOL for their important contributions. A complete list of staff and investigators has been provided by Sorlie P., et al. in Ann. Epidemiol. 2010 Aug;20: 642–649 and is also available on the study website http://www.cscc.unc.edu/hchs/. Other funding sources for this study include R01HL060712, R01HL140976, and R01HL136266 from the NHLBI; and R01DK119268, R01DK120870 and the New York Regional Center for Diabetes Translation Research (P30 DK111022) from the NIDDK. The Genetic Analysis Center at the University of Washington was supported by NHLBI and NIDCR contracts (HHSN268201300005C AM03 and MOD03). Genotyping efforts were supported by NHLBI HSN 26220/20054C, NCATS CTSI grant UL1TR000123, and NIDDK Diabetes Research Center (DRC) grant DK063491. The Arizona Insulin Resistance Registry: The AIR registry was supported by Health Research Alliance Arizona and the Center for Metabolic Biology at Arizona State University. Data management support was provided by a grant (UL1 RR024150) from the Mayo Clinic to utilize Research Electronic Data Capture (REDCap). Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

doi = "10.1038/s42003-021-02431-4",

language = "English (US)",

volume = "4",

journal = "Communications biology",

issn = "2399-3642",

publisher = "Springer Nature",

number = "1",

}

TY - JOUR

T1 - Impact of Amerind ancestry and FADS genetic variation on omega-3 deficiency and cardiometabolic traits in Hispanic populations

AU - Yang, Chaojie

AU - Hallmark, Brian

AU - Chai, Jin Choul

AU - O’Connor, Timothy D.

AU - Reynolds, Lindsay M.

AU - Wood, Alexis C.

AU - Seeds, Michael

AU - Chen, Yii Der Ida

AU - Steffen, Lyn M.

AU - Tsai, Michael Y.

AU - Kaplan, Robert C.

AU - Daviglus, Martha L.

AU - Mandarino, Lawrence J.

AU - Fretts, Amanda M.

AU - Lemaitre, Rozenn N.

AU - Coletta, Dawn K.

AU - Blomquist, Sarah A.

AU - Johnstone, Laurel M.

AU - Tontsch, Chandra

AU - Qi, Qibin

AU - Ruczinski, Ingo

AU - Rich, Stephen S.

AU - Mathias, Rasika A.

AU - Chilton, Floyd H.

AU - Manichaikul, Ani

N1 - Funding Information: This work was supported by NCCIH R01 AT008621 and USDA ARZT-1361680-H23-157. The Multi-Ethnic Study of Atherosclerosis: MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881, and DK063491. Funding for SHARe genotyping was provided by NHLBI Contract N02-HL-64278. Genotyping was performed at Affymetrix (Santa Clara, California, USA) and the Broad Institute of Harvard and MIT (Boston, Massachusetts, USA) using the Affymetrix Genome-Wide Human SNP Array 6.0. The Hispanic Community Health Study/Study of Latinos: HCHS/SOL is a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (HHSN268201300001I/N01-HC-65233), University of Miami (HHSN268201300004I/N01-HC-65234), Albert Einstein College of Medicine (HHSN268201300002I/N01-HC-65235), University of Illinois at Chicago (HHSN268201300003I/N01-HC-65236 Northwestern Univ), and San Diego State University (HHSN268201300005I/N01-HC-65237). The following Institutes/Centers/Offices have contributed to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Neurological Disorders and Stroke, and NIH Institution-Office of Dietary Supplements. The authors thank the staff and participants of HCHS/SOL for their important contributions. A complete list of staff and investigators has been provided by Sorlie P., et al. in Ann. Epidemiol. 2010 Aug;20: 642–649 and is also available on the study website http://www.cscc.unc.edu/hchs/. Other funding sources for this study include R01HL060712, R01HL140976, and R01HL136266 from the NHLBI; and R01DK119268, R01DK120870 and the New York Regional Center for Diabetes Translation Research (P30 DK111022) from the NIDDK. The Genetic Analysis Center at the University of Washington was supported by NHLBI and NIDCR contracts (HHSN268201300005C AM03 and MOD03). Genotyping efforts were supported by NHLBI HSN 26220/20054C, NCATS CTSI grant UL1TR000123, and NIDDK Diabetes Research Center (DRC) grant DK063491. The Arizona Insulin Resistance Registry: The AIR registry was supported by Health Research Alliance Arizona and the Center for Metabolic Biology at Arizona State University. Data management support was provided by a grant (UL1 RR024150) from the Mayo Clinic to utilize Research Electronic Data Capture (REDCap). Publisher Copyright: © 2021, The Author(s).

PY - 2021/12

Y1 - 2021/12

N2 - Long chain polyunsaturated fatty acids (LC-PUFAs) have critical signaling roles that regulate dyslipidemia and inflammation. Genetic variation in the FADS gene cluster accounts for a large portion of interindividual differences in circulating and tissue levels of LC-PUFAs, with the genotypes most strongly predictive of low LC-PUFA levels at strikingly higher frequencies in Amerind ancestry populations. In this study, we examined relationships between genetic ancestry and FADS variation in 1102 Hispanic American participants from the Multi-Ethnic Study of Atherosclerosis. We demonstrate strong negative associations between Amerind genetic ancestry and LC-PUFA levels. The FADS rs174537 single nucleotide polymorphism (SNP) accounted for much of the AI ancestry effect on LC-PUFAs, especially for low levels of n-3 LC-PUFAs. Rs174537 was also strongly associated with several metabolic, inflammatory and anthropomorphic traits including circulating triglycerides (TGs) and E-selectin in MESA Hispanics. Our study demonstrates that Amerind ancestry provides a useful and readily available tool to identify individuals most likely to have FADS-related n-3 LC-PUFA deficiencies and associated cardiovascular risk.

AB - Long chain polyunsaturated fatty acids (LC-PUFAs) have critical signaling roles that regulate dyslipidemia and inflammation. Genetic variation in the FADS gene cluster accounts for a large portion of interindividual differences in circulating and tissue levels of LC-PUFAs, with the genotypes most strongly predictive of low LC-PUFA levels at strikingly higher frequencies in Amerind ancestry populations. In this study, we examined relationships between genetic ancestry and FADS variation in 1102 Hispanic American participants from the Multi-Ethnic Study of Atherosclerosis. We demonstrate strong negative associations between Amerind genetic ancestry and LC-PUFA levels. The FADS rs174537 single nucleotide polymorphism (SNP) accounted for much of the AI ancestry effect on LC-PUFAs, especially for low levels of n-3 LC-PUFAs. Rs174537 was also strongly associated with several metabolic, inflammatory and anthropomorphic traits including circulating triglycerides (TGs) and E-selectin in MESA Hispanics. Our study demonstrates that Amerind ancestry provides a useful and readily available tool to identify individuals most likely to have FADS-related n-3 LC-PUFA deficiencies and associated cardiovascular risk.

UR - http://www.scopus.com/inward/record.url?scp=85111514986&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85111514986&partnerID=8YFLogxK

U2 - 10.1038/s42003-021-02431-4

DO - 10.1038/s42003-021-02431-4

M3 - Article

C2 - 34321601

AN - SCOPUS:85111514986

SN - 2399-3642

VL - 4

JO - Communications biology

JF - Communications biology

IS - 1

M1 - 918

ER -

Impact of Amerind ancestry and FADS genetic variation on omega-3 deficiency and cardiometabolic traits in Hispanic populations

Abstract

Bibliographical note

Publisher link

Find It

Other files and links

Fingerprint

Cite this