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Title: Analysis of the genetic basis of height in large Jewish nuclear families

Abstract

Despite intensive study, most of the specific genetic factors that contribute to variation in human height remain undiscovered. We conducted a family-based linkage study of height in a unique cohort of very large nuclear families from a founder (Jewish) population. This design allowed for increased power to detect linkage, compared to previous family-based studies. Loci we identified in discovery families could explain an estimated lower bound of 6% of the variance in height in validation families. We showed that these loci are not tagging known common variants associated with height. Rather, we suggest that the observed signals arise from variants with large effects that are rare globally but elevated in frequency in the Jewish population.

Authors:
ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1];  [2];  [3];  [4]; ORCiD logo [1]
  1. Univ. of California, Los Angeles, CA (United States). Dept. of Human Genetics; Univ. of California, Los Angeles, CA (United States). Dept. of Biological Chemistry; Univ. of California, Los Angeles, CA (United States). Howard Hughes Medical Inst.
  2. Shaare Zedek Medical Center, Jerusalem (Israel). Medical Genetics Inst.
  3. Hebrew Univ. of Jerusalem (Israel); Hadassah Hebrew Univ. Medical Center, Jerusalem (Israel). Division of Pediatric Endocrinology
  4. Shaare Zedek Medical Center, Jerusalem (Israel). Medical Genetics Inst.; Hebrew Univ. of Jerusalem (Israel)
Publication Date:
Research Org.:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1572032
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
PLoS Genetics
Additional Journal Information:
Journal Volume: 15; Journal Issue: 7; Journal ID: ISSN 1553-7404
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Zeevi, Danny, Bloom, Joshua S., Sadhu, Meru J., Ben Yehuda, Adi, Zangen, David, Levy-Lahad, Ephrat, and Kruglyak, Leonid. Analysis of the genetic basis of height in large Jewish nuclear families. United States: N. p., 2019. Web. doi:10.1371/journal.pgen.1008082.
Zeevi, Danny, Bloom, Joshua S., Sadhu, Meru J., Ben Yehuda, Adi, Zangen, David, Levy-Lahad, Ephrat, & Kruglyak, Leonid. Analysis of the genetic basis of height in large Jewish nuclear families. United States. https://doi.org/10.1371/journal.pgen.1008082
Zeevi, Danny, Bloom, Joshua S., Sadhu, Meru J., Ben Yehuda, Adi, Zangen, David, Levy-Lahad, Ephrat, and Kruglyak, Leonid. Mon . "Analysis of the genetic basis of height in large Jewish nuclear families". United States. https://doi.org/10.1371/journal.pgen.1008082. https://www.osti.gov/servlets/purl/1572032.
@article{osti_1572032,
title = {Analysis of the genetic basis of height in large Jewish nuclear families},
author = {Zeevi, Danny and Bloom, Joshua S. and Sadhu, Meru J. and Ben Yehuda, Adi and Zangen, David and Levy-Lahad, Ephrat and Kruglyak, Leonid},
abstractNote = {Despite intensive study, most of the specific genetic factors that contribute to variation in human height remain undiscovered. We conducted a family-based linkage study of height in a unique cohort of very large nuclear families from a founder (Jewish) population. This design allowed for increased power to detect linkage, compared to previous family-based studies. Loci we identified in discovery families could explain an estimated lower bound of 6% of the variance in height in validation families. We showed that these loci are not tagging known common variants associated with height. Rather, we suggest that the observed signals arise from variants with large effects that are rare globally but elevated in frequency in the Jewish population.},
doi = {10.1371/journal.pgen.1008082},
journal = {PLoS Genetics},
number = 7,
volume = 15,
place = {United States},
year = {Mon Jul 08 00:00:00 EDT 2019},
month = {Mon Jul 08 00:00:00 EDT 2019}
}

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Major Recessive Gene(s) with Considerable Residual Polygenic Effect Regulating Adult Height: Confirmation of Genomewide Scan Results for Chromosomes 6, 9, and 12
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Genetic Testing in Israel: An Overview
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A Genome-Wide Scan for Loci Affecting Normal Adult Height in the Framingham Heart Study
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Genome scan for body mass index and height in the Framingham Heart Study
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The impact of rare and low-frequency genetic variants in common disease
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Assumption-Free Estimation of Heritability from Genome-Wide Identity-by-Descent Sharing between Full Siblings
journal, January 2006


Combined Genome Scans for Body Stature in 6,602 European Twins: Evidence for Common Caucasian Loci
journal, January 2007


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Heritability of Adult Body Height: A Comparative Study of Twin Cohorts in Eight Countries
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Genotype Imputation with Thousands of Genomes
journal, November 2011

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