Leveraging population admixture to characterize the heritability of complex traits.
Despite recent progress on estimating the heritability explained by genotyped SNPs (h(2)g), a large gap between h(2)g and estimates of total narrow-sense heritability (h(2)) remains. Explanations for this gap include rare variants or upward bias in family-based estimates of h(2) due to shared environment or epistasis. We estimate h(2) from unrelated individuals in admixed populations by first estimating the heritability explained by local ancestry (h(2)γ). We show that h(2)γ = 2FSTCθ(1 - θ)h(2), where FSTC measures frequency differences between populations at causal loci and θ is the genome-wide ancestry proportion. Our approach is not susceptible to biases caused by epistasis or shared environment. We applied this approach to the analysis of 13 phenotypes in 21,497 African-American individuals from 3 cohorts. For height and body mass index (BMI), we obtained h(2) estimates of 0.55 ± 0.09 and 0.23 ± 0.06, respectively, which are larger than estimates of h(2)g in these and other data but smaller than family-based estimates of h(2).
Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Noah
N
Zaitlen
Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Bogdan
B
Pasaniuc
1] Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
Sriram
S
Sankararaman
1] Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. [2] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. [3] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
Gaurav
G
Bhatia
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Jianqi
J
Zhang
1] Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. [2] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. [3] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
Alexander
A
Gusev
Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Taylor
T
Young
1] Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
Arti
A
Tandon
1] Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. [2] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. [3] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
Samuela
S
Pollack
1] Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. [2] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. [3] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
Bjarni J
BJ
Vilhjálmsson
Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Themistocles L
TL
Assimes
Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
Sonja I
SI
Berndt
1] Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. [2] Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. [3] International Epidemiology Institute, Rockville, Maryland, USA.
William J
WJ
Blot
Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
Stephen
S
Chanock
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
Nora
N
Franceschini
SWOG Statistical Center, Seattle, Washington, USA.
Phyllis G
PG
Goodman
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Jing
J
He
1] Department of Preventive Medicine, Stony Brook University, Stony Brook, New York, USA. [2] Chronic Disease Research Centre, University of the West Indies, Bridgetown, Barbados. [3] Faculty of Medical Sciences, University of the West Indies, Bridgetown, Barbados. [4] Ministry of Health, Bridgetown, Barbados.
Anselm J M
AJ
Hennis
1] Cancer Prevention Institute of California, Fremont, California, USA. [2] Division of Epidemiology, Stanford University School of Medicine, Stanford, California, USA.
Ann
A
Hsing
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Sue A
SA
Ingles
James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institutions, Baltimore, Maryland, USA.
William
W
Isaacs
Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
Rick A
0000000250044437
RA
Kittles
Glickman Urologic and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Eric A
EA
Klein
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.
Leslie A
LA
Lange
Department of Preventive Medicine, Stony Brook University, Stony Brook, New York, USA.
Barbara
B
Nemesure
Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Nick
N
Patterson
1] Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA. [3] Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA.
David
D
Reich
Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan, USA.
Benjamin A
BA
Rybicki
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Janet L
JL
Stanford
Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA.
Victoria L
VL
Stevens
Department of Epidemiology, Division of Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Sara S
SS
Strom
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
Eric A
EA
Whitsel
Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.
John S
JS
Witte
Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Jianfeng
J
Xu
1] Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. [2] Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.
Christopher
C
Haiman
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA.
James G
JG
Wilson
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Charles
C
Kooperberg
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Daniel
0000000170999022
D
Stram
Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington, USA.
Alex P
AP
Reiner
Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
Hua
H
Tang
1] Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. [2] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. [3] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
Alkes L
AL
Price
D001741:Black or African American / Q000235:genetics; D000368:Aged; D044383:Black People; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000235:genetics; D016022:Case-Control Studies; D002874:Chromosome Mapping; D015331:Cohort Studies; D003198:Computer Simulation; D004843:Epistasis, Genetic; D005260:Female; D005828:Genetics, Population / Q000379:methods*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D015233:Models, Statistical; D020412:Multifactorial Inheritance; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics; D019655:Quantitative Trait, Heritable; D015203:Reproducibility of Results; D014481:United States