Evidence map›Paper›PMID 33987664›Full record

ArticleHuman molecular genetics2021

Estimating heritability and its enrichment in tissue-specific gene sets in admixed populations.

Yang Luo, Xinyi Li, Xin Wang, Steven Gazal, Josep Maria Mercader, 23 and Me Research Team, SIGMA Type 2 Diabetes Consortium, Benjamin M Neale, Jose C Florez, Adam Auton and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human molecular genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 16 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 16 pooled it
7.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

68 citing papers in PubMed, 16 syntheses or guidelines pooled it, 56 citations in OpenAlex.

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  6. Multiancestry Transcriptome-Wide Association Study Identifies Candidate Genes Associated with Hepatoblastoma.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025
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  14. Cross-phenotype association analysis of gastric cancer: in-silico functional annotation based on the disease-gene network.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2023
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  19. Type 2 diabetes genetics in 125,000 admixed adults from Mexico City.medRxiv : the preprint server for health sciences · 2026
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8 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 2 countries.

Yang LuoCenter for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Xinyi LiCenter for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Xin Wang23andMe, Inc., Mountain View, California, USA.
Steven GazalBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Josep Maria MercaderDivision of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
23 and Me Research Team
SIGMA Type 2 Diabetes Consortium
Benjamin M NealeBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Jose C FlorezBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Adam Auton23andMe, Inc., Mountain View, California, USA.
Alkes L PriceBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Hilary K FinucaneBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Soumya RaychaudhuriCenter for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Broad Institute · US23andMe (United States) · USBrigham and Women's Hospital · US

Funding

Metabolomics Core U19AI111224 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI MOODY, DAVID BRANCH, MURRAY, MEGAN B · 2015 to 2021
$20.4M
Statistical methods to localize disease heritability and identify biological mechanismsR37MH107649 · NIMH · BROAD INSTITUTE, INC. · PI Benjamin Michael Neale · 2019 to 2026
$7.0M
Powering whole genome sequence-based genetic discovery for common human diseases- Extended 2021-2022.U01HG009088 · NHGRI · HARVARD SCHOOL OF PUBLIC HEALTH · PI LIN, XIHONG, NEALE, BENJAMIN MICHAEL · 2016 to 2021
$5.1M
Functionally specialized components of disease heritability in ENCODE dataU01HG009379 · NHGRI · HARVARD SCHOOL OF PUBLIC HEALTH · PI PRICE, ALKES L, RAYCHAUDHURI, SOUMYA · 2017 to 2021
$2.5M
23andMe cohortNHGRI NIH HHS U01 HG009088NHGRI NIH HHS U01 HG009379NIAID NIH HHS U19 AI111224NIH HHS R37 MH107649NIMH NIH HHS R37 MH107649Sigma Theta Tau International
6 · The paper itself

Abstract

It is important to study the genetics of complex traits in diverse populations. Here, we introduce covariate-adjusted linkage disequilibrium (LD) score regression (cov-LDSC), a method to estimate SNP-heritability (${\boldsymbol{h}}_{\boldsymbol{g}}^{\mathbf{2}})$ and its enrichment in homogenous and admixed populations with summary statistics and in-sample LD estimates. In-sample LD can be estimated from a subset of the genome-wide association studies samples, allowing our method to be applied efficiently to very large cohorts. In simulations, we show that unadjusted LDSC underestimates ${\boldsymbol{h}}_{\boldsymbol{g}}^{\mathbf{2}}$ by 10-60% in admixed populations; in contrast, cov-LDSC is robustly accurate. We apply cov-LDSC to genotyping data from 8124 individuals, mostly of admixed ancestry, from the Slim Initiative in Genomic Medicine for the Americas study, and to approximately 161 000 Latino-ancestry individuals, 47 000 African American-ancestry individuals and 135 000 European-ancestry individuals, as classified by 23andMe. We estimate ${\boldsymbol{h}}_{\boldsymbol{g}}^{\mathbf{2}}$ and detect heritability enrichment in three quantitative and five dichotomous phenotypes, making this, to our knowledge, the most comprehensive heritability-based analysis of admixed individuals to date. Most traits have high concordance of ${\boldsymbol{h}}_{\boldsymbol{g}}^{\mathbf{2}}$ and consistent tissue-specific heritability enrichment among different populations. However, for age at menarche, we observe population-specific heritability estimates of ${\boldsymbol{h}}_{\boldsymbol{g}}^{\mathbf{2}}$. We observe consistent patterns of tissue-specific heritability enrichment across populations; for example, in the limbic system for BMI, the per-standardized-annotation effect size $ \tau $* is 0.16 ± 0.04, 0.28 ± 0.11 and 0.18 ± 0.03 in the Latino-, African American- and European-ancestry populations, respectively. Our approach is a powerful way to analyze genetic data for complex traits from admixed populations.

Indexed as

Genetics, PopulationGenome-Wide Association StudyGenotyping TechniquesHumansLinkage DisequilibriumMultifactorial InheritancePhenotypePolymorphism, Single NucleotideQuantitative Trait, Heritable

Identifiers

PMID33987664
PMCPMC8330913
OpenAlexW3160007175

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.