Correlations between complex human phenotypes vary by genetic background, gender, and environment

被引：9

作者：

Elgart, Michael ^{[1
,2
]}

Goodman, Matthew O. ^{[1
,2
]}

Isasi, Carmen ^{[3
]}

Chen, Han ^{[4
,5
]}

Morrison, Alanna C. ^{[4
]}

de Vries, Paul S. ^{[4
]}

Xu, Huichun ^{[6
]}

Manichaikul, Ani W. ^{[7
]}

Guo, Xiuqing ^{[8
]}

Franceschini, Nora ^{[9
]}

Psaty, Bruce M. ^{[10
,11
,12
]}

Rich, Stephen S. ^{[13
]}

Rotter, Jerome I. ^{[8
]}

Lloyd-Jones, Donald M. ^{[14
]}

Fornage, Myriam ^{[4
,15
]}

Correa, Adolfo ^{[16
]}

Heard-Costa, Nancy L. ^{[17
,18
,19
]}

Vasan, Ramachandran S. ^{[17
,18
,20
]}

Hernandez, Ryan ^{[21
]}

Kaplan, Robert C. ^{[3
,22
]}

Redline, Susan ^{[1
,2
]}

Sofer, Tamar ^{[1
,2
,23
]}

机构：

[1] Brigham & Womens Hosp, Div Sleep & Circadian Disorders, Boston, MA 02115 USA

[2] Harvard Med Sch, Dept Med, Boston, MA 02115 USA

[3] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY USA

[4] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Houston, TX USA

[5] Univ Texas Hlth Sci Ctr Houston, Ctr Precis Hlth, Sch Biomed Informat, Houston, TX USA

[6] Univ Maryland, Sch Med, Dept Med, Baltimore, MD USA

[7] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA

[8] Harbor UCLA Med Ctr, Lundquist Inst Biomed Innovat, Inst Translat Genom & Populat Sci, Dept Pediat, Torrance, CA USA

[9] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA

[10] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Cardiovasc Med,Med,Epidemiol, Seattle, WA USA

[11] Univ Washington, Dept Epidemiol, Seattle, WA USA

[12] Univ Washington, Dept Hlth Serv, Seattle, WA USA

[13] Univ Virginia, Ctr Publ Hlth Genom, Sch Med, Charlottesville, VA 02115 USA

[14] Northwestern Univ, Dept Prevent Med, Chicago, IL USA

[15] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, McGovern Med Sch, Houston, TX USA

[16] Univ Mississippi, Med Ctr, Dept Populat Hlth Sci, Jackson, MS USA

[17] Boston Univ, Framingham, MA USA

[18] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA

[19] Boston Univ, Sch Med, Dept Neurol, Boston, MA USA

[20] Boston Univ, Sch Med & Epidemiol, Prevent Med & Epidemiol & Cardiovasc Med, Med, Boston, MA USA

[21] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA USA

[22] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA USA

[23] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA

来源：

CELL REPORTS MEDICINE | 2022年 / 3卷 / 12期

关键词：

GENOMIC RELATIONSHIPS; SCORE REGRESSION; SEX-DIFFERENCES; HERITABILITY; ARCHITECTURE; HEALTH; POPULATION; DESIGN; INFERENCE; DISEASES;

D O I：

10.1016/j.xcrm.2022.100844

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

We develop a closed-form Haseman-Elston estimator for genetic and environmental correlation coefficients between complex phenotypes, which we term HEc, that is as precise as GCTA yet -203 faster. We estimate genetic and environmental correlations between over 7,000 phenotype pairs in subgroups from the TransOmics in Precision Medicine (TOPMed) program. We demonstrate substantial differences in both heritabilities and genetic correlations for multiple phenotypes and phenotype pairs between individuals of self-reported Black, Hispanic/Latino, and White backgrounds. We similarly observe differences in many of the genetic and environmental correlations between genders. To estimate the contribution of genetics to the observed phenotypic correlation, we introduce "fractional genetic correlation"as the fraction of phenotypic correlation explained by genetics. Finally, we quantify the enrichment of correlations between phenotypic domains, each of which is comprised of multiple phenotypes. Altogether, we demonstrate that the observed correlations between complex human phenotypes depend on the genetic background of the individuals, their gender, and their environment.

引用

页数：22

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