Variant level heritability estimates of type 2 diabetes in African Americans

Nicole D. Armstrong; Amit Patki; Vinodh Srinivasasainagendra; Tian Ge; Leslie A. Lange; Leah Kottyan; Bahram Namjou; Amy S. Shah; Laura J. Rasmussen-Torvik; Gail P. Jarvik; James B. Meigs; Elizabeth W. Karlson; Nita A. Limdi; Marguerite R. Irvin; Hemant K. Tiwari

doi:10.1038/s41598-024-64711-3

Variant level heritability estimates of type 2 diabetes in African Americans

Nicole D. Armstrong^*, Amit Patki, Vinodh Srinivasasainagendra, Tian Ge, Leslie A. Lange, Leah Kottyan, Bahram Namjou, Amy S. Shah, Laura J. Rasmussen-Torvik, Gail P. Jarvik, James B. Meigs, Elizabeth W. Karlson, Nita A. Limdi, Marguerite R. Irvin, Hemant K. Tiwari

^*Corresponding author for this work

Preventive Medicine

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

Abstract

Type 2 diabetes (T2D) is caused by both genetic and environmental factors and is associated with an increased risk of cardiorenal complications and mortality. Though disproportionately affected by the condition, African Americans (AA) are largely underrepresented in genetic studies of T2D, and few estimates of heritability have been calculated in this race group. Using genome-wide association study (GWAS) data paired with phenotypic data from ~ 19,300 AA participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, Genetics of Hypertension Associated Treatments (GenHAT) study, and the Electronic Medical Records and Genomics (eMERGE) network, we estimated narrow-sense heritability using two methods: Linkage-Disequilibrium Adjusted Kinships (LDAK) and Genome-Wide Complex Trait Analysis (GCTA). Study-level heritability estimates adjusting for age, sex, and genetic ancestry ranged from 18% to 34% across both methods. Overall, the current study narrows the expected range for T2D heritability in this race group compared to prior estimates, while providing new insight into the genetic basis of T2D in AAs for ongoing genetic discovery efforts.

Original language	English (US)
Article number	14009
Journal	Scientific reports
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41598-024-64711-3
State	Published - Dec 2024

Funding

The eMERGE Network was funded by the National Human Genome Research Institute (NHGRI) through the following grants: U01HG006828 (Cincinnati Children's Hospital Medical Center and Boston Children\u2019s Hospital); U01HG006830 (Children\u2019s Hospital of Philadelphia); U01HG006389 (Essentia Institute of Rural Health, Marshfield Clinic Research Foundation, and Pennsylvania State University); U01HG006382 (Geisinger Clinic); U01HG006375 (Group Health Cooperative and the University of Washington); U01HG006379 (Mayo Clinic); U01HG006380 (Icahn School of Medicine at Mount Sinai); U01HG006388 (Northwestern University); U01HG006378 (Vanderbilt University Medical Center); and U01HG006385 (Vanderbilt University Medical Center serving as the Coordinating Center). The eMERGE IV Mass General Brigham site was funded by the NHGRI through U01HG008685, the Columbia University site was funded through U01HG008680, and the University of Alabama at Birmingham site was funded through U01HG011167. The REGARDS (R01HL136666, MRI, LAL) and GenHAT (R01HL123782, MRI) genetic studies were supported by the National Heart, Lung, and Blood Institute (NHLBI). The parent REGARDS study was supported by cooperative agreement U01 NS041588, co-funded by the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute on Aging (NIA).The content is solely the responsibility of the authors and does not necessarily represent the official views of the NINDS or the NIA. Representatives of the NINDS were involved in the review of the manuscript but were not directly involved in the collection, management, analysis, or interpretation of the data. Other funding sources include NHLBI T32HL072757 (N.D.A.), UM1 DK078616 (J.B.M.) R01HL151855 (J.B.M.), R01HL092173 (N.A.L.), and R00AG054573 (T.G.).

Keywords

Disparities
Genetic polymorphisms
Genomics
Heritable quantitative trait
Type 2 diabetes mellitus

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41598-024-64711-3

Cite this

Armstrong, N. D., Patki, A., Srinivasasainagendra, V., Ge, T., Lange, L. A., Kottyan, L., Namjou, B., Shah, A. S., Rasmussen-Torvik, L. J., Jarvik, G. P., Meigs, J. B., Karlson, E. W., Limdi, N. A., Irvin, M. R., & Tiwari, H. K. (2024). Variant level heritability estimates of type 2 diabetes in African Americans. Scientific reports, 14(1), Article 14009. https://doi.org/10.1038/s41598-024-64711-3

@article{1fdd0fc027214dae80dc717e170665eb,

title = "Variant level heritability estimates of type 2 diabetes in African Americans",

abstract = "Type 2 diabetes (T2D) is caused by both genetic and environmental factors and is associated with an increased risk of cardiorenal complications and mortality. Though disproportionately affected by the condition, African Americans (AA) are largely underrepresented in genetic studies of T2D, and few estimates of heritability have been calculated in this race group. Using genome-wide association study (GWAS) data paired with phenotypic data from ~ 19,300 AA participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, Genetics of Hypertension Associated Treatments (GenHAT) study, and the Electronic Medical Records and Genomics (eMERGE) network, we estimated narrow-sense heritability using two methods: Linkage-Disequilibrium Adjusted Kinships (LDAK) and Genome-Wide Complex Trait Analysis (GCTA). Study-level heritability estimates adjusting for age, sex, and genetic ancestry ranged from 18% to 34% across both methods. Overall, the current study narrows the expected range for T2D heritability in this race group compared to prior estimates, while providing new insight into the genetic basis of T2D in AAs for ongoing genetic discovery efforts.",

keywords = "Disparities, Genetic polymorphisms, Genomics, Heritable quantitative trait, Type 2 diabetes mellitus",

author = "Armstrong, {Nicole D.} and Amit Patki and Vinodh Srinivasasainagendra and Tian Ge and Lange, {Leslie A.} and Leah Kottyan and Bahram Namjou and Shah, {Amy S.} and Rasmussen-Torvik, {Laura J.} and Jarvik, {Gail P.} and Meigs, {James B.} and Karlson, {Elizabeth W.} and Limdi, {Nita A.} and Irvin, {Marguerite R.} and Tiwari, {Hemant K.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = dec,

doi = "10.1038/s41598-024-64711-3",

language = "English (US)",

volume = "14",

journal = "Scientific reports",

issn = "2045-2322",

publisher = "Nature Research",

number = "1",

}

TY - JOUR

T1 - Variant level heritability estimates of type 2 diabetes in African Americans

AU - Armstrong, Nicole D.

AU - Patki, Amit

AU - Srinivasasainagendra, Vinodh

AU - Ge, Tian

AU - Lange, Leslie A.

AU - Kottyan, Leah

AU - Namjou, Bahram

AU - Shah, Amy S.

AU - Rasmussen-Torvik, Laura J.

AU - Jarvik, Gail P.

AU - Meigs, James B.

AU - Karlson, Elizabeth W.

AU - Limdi, Nita A.

AU - Irvin, Marguerite R.

AU - Tiwari, Hemant K.

PY - 2024/12

Y1 - 2024/12

N2 - Type 2 diabetes (T2D) is caused by both genetic and environmental factors and is associated with an increased risk of cardiorenal complications and mortality. Though disproportionately affected by the condition, African Americans (AA) are largely underrepresented in genetic studies of T2D, and few estimates of heritability have been calculated in this race group. Using genome-wide association study (GWAS) data paired with phenotypic data from ~ 19,300 AA participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, Genetics of Hypertension Associated Treatments (GenHAT) study, and the Electronic Medical Records and Genomics (eMERGE) network, we estimated narrow-sense heritability using two methods: Linkage-Disequilibrium Adjusted Kinships (LDAK) and Genome-Wide Complex Trait Analysis (GCTA). Study-level heritability estimates adjusting for age, sex, and genetic ancestry ranged from 18% to 34% across both methods. Overall, the current study narrows the expected range for T2D heritability in this race group compared to prior estimates, while providing new insight into the genetic basis of T2D in AAs for ongoing genetic discovery efforts.

AB - Type 2 diabetes (T2D) is caused by both genetic and environmental factors and is associated with an increased risk of cardiorenal complications and mortality. Though disproportionately affected by the condition, African Americans (AA) are largely underrepresented in genetic studies of T2D, and few estimates of heritability have been calculated in this race group. Using genome-wide association study (GWAS) data paired with phenotypic data from ~ 19,300 AA participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, Genetics of Hypertension Associated Treatments (GenHAT) study, and the Electronic Medical Records and Genomics (eMERGE) network, we estimated narrow-sense heritability using two methods: Linkage-Disequilibrium Adjusted Kinships (LDAK) and Genome-Wide Complex Trait Analysis (GCTA). Study-level heritability estimates adjusting for age, sex, and genetic ancestry ranged from 18% to 34% across both methods. Overall, the current study narrows the expected range for T2D heritability in this race group compared to prior estimates, while providing new insight into the genetic basis of T2D in AAs for ongoing genetic discovery efforts.

KW - Disparities

KW - Genetic polymorphisms

KW - Genomics

KW - Heritable quantitative trait

KW - Type 2 diabetes mellitus

UR - http://www.scopus.com/inward/record.url?scp=85196266320&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85196266320&partnerID=8YFLogxK

U2 - 10.1038/s41598-024-64711-3

DO - 10.1038/s41598-024-64711-3

M3 - Article

C2 - 38890458

AN - SCOPUS:85196266320

SN - 2045-2322

VL - 14

JO - Scientific reports

JF - Scientific reports

IS - 1

M1 - 14009

ER -

Variant level heritability estimates of type 2 diabetes in African Americans

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this