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

Zeevi, Danny; Bloom, Joshua S.; Sadhu, Meru J.; Ben Yehuda, Adi; Zangen, David; Levy-Lahad, Ephrat; Kruglyak, Leonid

doi:10.1371/journal.pgen.1008082

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

Journal Article · Mon Jul 08 00:00:00 EDT 2019 · PLoS Genetics

DOI:https://doi.org/10.1371/journal.pgen.1008082· OSTI ID:1572032

^[1];

^[1]; Ben Yehuda, Adi ^[2]; Zangen, David ^[3]; Levy-Lahad, Ephrat ^[4];

^[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.
Shaare Zedek Medical Center, Jerusalem (Israel). Medical Genetics Inst.
Hebrew Univ. of Jerusalem (Israel); Hadassah Hebrew Univ. Medical Center, Jerusalem (Israel). Division of Pediatric Endocrinology
Shaare Zedek Medical Center, Jerusalem (Israel). Medical Genetics Inst.; Hebrew Univ. of Jerusalem (Israel)

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.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1572032

Journal Information:: PLoS Genetics, Vol. 15, Issue 7; ISSN 1553-7404

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 1 work

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References (61)

Accurate Non-parametric Estimation of Recent Effective Population Size from Segments of Identity by Descent Browning, Sharon R.; Browning, Brian L. The American Journal of Human Genetics, Vol. 97, Issue 3 https://doi.org/10.1016/j.ajhg.2015.07.012	journal	September 2015
Linkage analysis of quantitative traits for obesity, diabetes, hypertension, and dyslipidemia on the island of Kosrae, Federated States of Micronesia Shmulewitz, D.; Heath, S. C.; Blundell, M. L. Proceedings of the National Academy of Sciences, Vol. 103, Issue 10 https://doi.org/10.1073/pnas.0510156103	journal	February 2006
Genetic identification of a common collagen disease in Puerto Ricans via identity-by-descent mapping in a health system Belbin, Gillian Morven; Odgis, Jacqueline; Sorokin, Elena P. eLife, Vol. 6 https://doi.org/10.7554/eLife.25060	journal	September 2017
Statistical power and significance testing in large-scale genetic studies Sham, Pak C.; Purcell, Shaun M. Nature Reviews Genetics, Vol. 15, Issue 5 https://doi.org/10.1038/nrg3706	journal	April 2014
Height-reducing variants and selection for short stature in Sardinia Zoledziewska, Magdalena; Sidore, Carlo; Chiang, Charleston W. K. Nature Genetics, Vol. 47, Issue 11 https://doi.org/10.1038/ng.3403	journal	September 2015
Disruption of the p70s6k/p85s6k gene reveals a small mouse phenotype and a new functional S6 kinase Shima, H. The EMBO Journal, Vol. 17, Issue 22 https://doi.org/10.1093/emboj/17.22.6649	journal	November 1998
Controlling the Rate of GWAS False Discoveries Brzyski, Damian; Peterson, Christine B.; Sobczyk, Piotr Genetics, Vol. 205, Issue 1 https://doi.org/10.1534/genetics.116.193987	journal	October 2016
A global reference for human genetic variation Consortium, The 1000 Genomes Project; Auton, Adam; Abecasis, Gonçalo R. Nature, Vol. 526, Issue 7571, p. 68-74 https://doi.org/10.1038/nature15393	journal	January 2015
The impact of rare and low-frequency genetic variants in common disease Bomba, Lorenzo; Walter, Klaudia; Soranzo, Nicole Genome Biology, Vol. 18, Issue 1 https://doi.org/10.1186/s13059-017-1212-4	journal	April 2017
A whole-genome linkage scan suggests several genomic regions potentially containing QTLs underlying the variation of stature Deng, Hong-Wen; Xu, Fu-Hua; Liu, Yao-Zhong American Journal of Medical Genetics, Vol. 113, Issue 1 https://doi.org/10.1002/ajmg.10742	journal	November 2002
Combined analysis of genomewide scans for adult height: results from the NHLBI Family Blood Pressure Program Wu, Xiaodong; Cooper, Richard S.; Boerwinkle, Eric European Journal of Human Genetics, Vol. 11, Issue 3 https://doi.org/10.1038/sj.ejhg.5200952	journal	March 2003
Combined Genome Scans for Body Stature in 6,602 European Twins: Evidence for Common Caucasian Loci Perola, Markus; Sammalisto, Sampo; Hiekkalinna, Tero PLoS Genetics, Vol. 3, Issue 6 https://doi.org/10.1371/journal.pgen.0030097	journal	January 2007
Genetic Testing in Israel: An Overview Rosner, Guy; Rosner, Serena; Orr-Urtreger, Avi Annual Review of Genomics and Human Genetics, Vol. 10, Issue 1 https://doi.org/10.1146/annurev.genom.030308.111406	journal	September 2009
Personal genomes: The case of the missing heritability Maher, Brendan Nature, Vol. 456, Issue 7218 https://doi.org/10.1038/456018a	journal	November 2008
Searching for missing heritability: Designing rare variant association studies Zuk, O.; Schaffner, S. F.; Samocha, K. Proceedings of the National Academy of Sciences, Vol. 111, Issue 4 https://doi.org/10.1073/pnas.1322563111	journal	January 2014
Comprehensive multi-stage linkage analyses identify a locus for adult height on chromosome 3p in a healthy Caucasian population Ellis, Justine A.; Scurrah, Katrina J.; Duncan, Anna E. Human Genetics, Vol. 121, Issue 2 https://doi.org/10.1007/s00439-006-0305-z	journal	December 2006
Major Recessive Gene(s) with Considerable Residual Polygenic Effect Regulating Adult Height: Confirmation of Genomewide Scan Results for Chromosomes 6, 9, and 12 Xu, Jianfeng; Bleecker, Eugene R.; Jongepier, Hajo The American Journal of Human Genetics, Vol. 71, Issue 3 https://doi.org/10.1086/342216	journal	September 2002
Genotype Imputation with Thousands of Genomes Howie, Bryan; Marchini, Jonathan; Stephens, Matthew G3: Genes\|Genomes\|Genetics, Vol. 1, Issue 6 https://doi.org/10.1534/g3.111.001198	journal	November 2011
Age-Stratified QTL Genome Scan Analyses for Anthropometric Measures Beck, Stephanie R.; Brown, W. Mark; Williams, Adrienne H. BMC Genetics, Vol. 4, Issue Suppl 1 https://doi.org/10.1186/1471-2156-4-S1-S31	journal	January 2003
Genomewide Linkage Analysis of Stature in Multiple Populations Reveals Several Regions with Evidence of Linkage to Adult Height Hirschhorn, Joel N.; Lindgren, Cecilia M.; Daly, Mark J. The American Journal of Human Genetics, Vol. 69, Issue 1 https://doi.org/10.1086/321287	journal	July 2001
GCTA: A Tool for Genome-wide Complex Trait Analysis Yang, Jian; Lee, S. Hong; Goddard, Michael E. The American Journal of Human Genetics, Vol. 88, Issue 1 https://doi.org/10.1016/j.ajhg.2010.11.011	journal	January 2011
Quantitative-Trait-Locus Analysis of Body-Mass Index and of Stature, by Combined Analysis of Genome Scans of Five Finnish Study Groups Perola, Markus; Öhman, Miina; Hiekkalinna, Tero The American Journal of Human Genetics, Vol. 69, Issue 1 https://doi.org/10.1086/321286	journal	July 2001
The use of a genetic map of biallelic markers in linkage studies Kruglyak, Leonid Nature Genetics, Vol. 17, Issue 1 https://doi.org/10.1038/ng0997-21	journal	September 1997
Loci Contributing to Adult Height and Body Mass Index in African American Families Ascertained for Type 2 Diabetes Sale, M. M.; Freedman, B. I.; Hicks, P. J. Annals of Human Genetics, Vol. 69, Issue 5 https://doi.org/10.1046/j.1529-8817.2005.00176.x	journal	September 2005
Genome-wide linkage screen for stature and body mass index in 3.032 families: evidence for sex- and population-specific genetic effects Sammalisto, Sampo; Hiekkalinna, Tero; Schwander, Karen European Journal of Human Genetics, Vol. 17, Issue 2 https://doi.org/10.1038/ejhg.2008.152	journal	September 2008
Evidence for Linkage of Stature to Chromosome 3p26 in a Large U.K. Family Data Set Ascertained for Type 2 Diabetes Wiltshire, Steven; Frayling, Timothy M.; Hattersley, Andrew T. The American Journal of Human Genetics, Vol. 70, Issue 2 https://doi.org/10.1086/338760	journal	February 2002
A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes Moltke, Ida; Grarup, Niels; Jørgensen, Marit E. Nature, Vol. 512, Issue 7513 https://doi.org/10.1038/nature13425	journal	June 2014
Analysis of protein-coding genetic variation in 60,706 humans Lek, Monkol; Karczewski, Konrad J.; Minikel, Eric V. Nature, Vol. 536, Issue 7616 https://doi.org/10.1038/nature19057	journal	August 2016
Assumption-Free Estimation of Heritability from Genome-Wide Identity-by-Descent Sharing between Full Siblings Visscher, Peter M.; Medland, Sarah E.; Ferreira, Manuel A. R. PLoS Genetics, Vol. 2, Issue 3 https://doi.org/10.1371/journal.pgen.0020041	journal	January 2006
Common variants in the JAZF1 gene associated with height identified by linkage and genome-wide association analysis Johansson, Åsa; Marroni, Fabio; Hayward, Caroline Human Molecular Genetics, Vol. 18, Issue 2 https://doi.org/10.1093/hmg/ddn350	journal	October 2008
A Genome-Wide Scan for Loci Affecting Normal Adult Height in the Framingham Heart Study Mukhopadhyay, Nandita; Finegold, David N.; Larson, Martin G. Human Heredity, Vol. 55, Issue 4 https://doi.org/10.1159/000073203	journal	January 2003
Genetic Dissection of Human Stature in a Large Sample of Multiplex Pedigrees: Linkage Study of Stature Liu, Yao-Zhong; Xu, Fu-Hua; Shen, Hui Annals of Human Genetics, Vol. 68, Issue 5 https://doi.org/10.1046/j.1529-8817.2003.00117.x	journal	August 2004
Sequencing an Ashkenazi reference panel supports population-targeted personal genomics and illuminates Jewish and European origins Carmi, Shai; Hui, Ken Y.; Kochav, Ethan Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms5835	journal	September 2014
Inference of the Genetic Architecture Underlying BMI and Height with the Use of 20,240 Sibling Pairs Hemani, Gibran; Yang, Jian; Vinkhuyzen, Anna The American Journal of Human Genetics, Vol. 93, Issue 5 https://doi.org/10.1016/j.ajhg.2013.10.005	journal	November 2013
Drosophila S6 Kinase: A Regulator of Cell Size Montagne, J. Science, Vol. 285, Issue 5436 https://doi.org/10.1126/science.285.5436.2126	journal	September 1999
A genetic profile of contemporary Jewish populations Ostrer, Harry Nature Reviews Genetics, Vol. 2, Issue 11 https://doi.org/10.1038/35098506	journal	November 2001
Evidence for involvement of the vitamin D receptor gene in idiopathic short stature via a genome-wide linkage study and subsequent association studies Dempfle, Astrid; Wudy, Stefan A.; Saar, Kathrin Human Molecular Genetics, Vol. 15, Issue 18 https://doi.org/10.1093/hmg/ddl218	journal	August 2006
Molecular genetics of pecanex, a maternal-effect neurogenic locus of Drosophila melanogaster that potentially encodes a large transmembrane protein LaBonne, Stephen G.; Sunitha, I.; Mahowald, Anthony P. Developmental Biology, Vol. 136, Issue 1 https://doi.org/10.1016/0012-1606(89)90127-9	journal	November 1989
QTLs for height: results of a full genome scan in Dutch sibling pairs Willemsen, Gonneke; Boomsma, Dorret I.; Beem, A. Leo European Journal of Human Genetics, Vol. 12, Issue 10 https://doi.org/10.1038/sj.ejhg.5201229	journal	August 2004
The effective size of the Icelandic population and the prospects for LD mapping: inference from unphased microsatellite markers Bataillon, Thomas; Mailund, Thomas; Thorlacius, Steinunn European Journal of Human Genetics, Vol. 14, Issue 9 https://doi.org/10.1038/sj.ejhg.5201669	journal	May 2006
Multipoint Quantitative-Trait Linkage Analysis in General Pedigrees Almasy, Laura; Blangero, John The American Journal of Human Genetics, Vol. 62, Issue 5 https://doi.org/10.1086/301844	journal	May 1998
Defining the role of common variation in the genomic and biological architecture of adult human height Wood, Andrew R.; Esko, Tonu; Yang, Jian Nature Genetics, Vol. 46, Issue 11 https://doi.org/10.1038/ng.3097	journal	October 2014
Genetic linkage of human height is confirmed to 9q22 and Xq24 Liu, Yao-Zhong; Xiao, Peng; Guo, Yan-fang Human Genetics, Vol. 119, Issue 3 https://doi.org/10.1007/s00439-006-0136-y	journal	January 2006
Longitudinal Change in Height of Men and Women: Implications for Interpretation of the Body Mass Index: The Baltimore Longitudinal Study of Aging Sorkin, J. D.; Muller, D. C.; Andres, R. American Journal of Epidemiology, Vol. 150, Issue 9 https://doi.org/10.1093/oxfordjournals.aje.a010106	journal	November 1999
Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results Lander, Eric; Kruglyak, Leonid Nature Genetics, Vol. 11, Issue 3 https://doi.org/10.1038/ng1195-241	journal	November 1995
Pecanex functions as a competitive endogenous RNA of S-phase kinase associated protein 2 in lung cancer Li, Jingqiu; Tian, Haihua; Pan, Jinchang Cancer Letters, Vol. 406 https://doi.org/10.1016/j.canlet.2017.07.030	journal	October 2017
Heritability of Adult Body Height: A Comparative Study of Twin Cohorts in Eight Countries Silventoinen, Karri; Sammalisto, Sampo; Perola, Markus Twin Research, Vol. 6, Issue 5 https://doi.org/10.1375/136905203770326402	journal	October 2003
The genome-wide structure of the Jewish people Behar, Doron M.; Yunusbayev, Bayazit; Metspalu, Mait Nature, Vol. 466, Issue 7303 https://doi.org/10.1038/nature09103	journal	June 2010
The Architecture of Long-Range Haplotypes Shared within and across Populations Gusev, A.; Palamara, P. F.; Aponte, G. Molecular Biology and Evolution, Vol. 29, Issue 2 https://doi.org/10.1093/molbev/msr133	journal	October 2011
Raptor, a Binding Partner of Target of Rapamycin (TOR), Mediates TOR Action Hara, Kenta; Maruki, Yoshiko; Long, Xiaomeng Cell, Vol. 110, Issue 2 https://doi.org/10.1016/S0092-8674(02)00833-4	journal	July 2002
Identification of deleterious recessive haplotypes and candidate deleterious recessive mutations in Japanese Black cattle Sasaki, Shinji; Watanabe, Toshio; Ibi, Takayuki Scientific Reports, Vol. 11, Issue 1 https://doi.org/10.1038/s41598-021-86225-y	journal	March 2021
Defining the role of common variation in the genomic and biological architecture of adult human height André, Scherag,; Y., Chu, Audrey; Tonu, Esko, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/3109-8m43	text	January 2014
A global reference for human genetic variation Xiaosen, Guo,; Meifang, Tang,; Tianming, Lan, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/0ez3-8z76	text	January 2015
Genetic identification of a common collagen disease in Puerto Ricans via identity-by-descent mapping in a health system Lucia, Hindorff,; Jacqueline, Odgis,; Ulrike, Peters, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/mv5t-7356	text	January 2017
Analysis of protein-coding genetic variation in 60,706 humans Aarno, Palotie,; A., Rivas, Manuel; Hong-Hee, Won, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/akst-av84	text	January 2016
A global reference for human genetic variation Yun, Li, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/p70n-j697	text	January 2015
Geographic variation in the polygenic score of height in Japan Isshiki, Mariko; Watanabe, Yusuke; Ohashi, Jun Human Genetics, Vol. 140, Issue 7 https://doi.org/10.1007/s00439-021-02281-4	journal	April 2021
Rare and low-frequency coding variants alter human adult height Marouli, Eirini; Graff, Mariaelisa; Medina-Gomez, Carolina Nature, Vol. 542, Issue 7640 https://doi.org/10.1038/nature21039	journal	February 2017
All LODs Are Not Created Equal**A Microsoft Excel spreadsheet, for performing easy calculations of P values for the LOD scores described in this review, is available on request from the author. Nyholt, Dale R. The American Journal of Human Genetics, Vol. 67, Issue 2 https://doi.org/10.1086/303029	journal	August 2000
Genome scan for body mass index and height in the Framingham Heart Study Geller, Frank; Dempfle, Astrid; Görg, Tilman BMC Genetics, Vol. 4, Issue Suppl 1 https://doi.org/10.1186/1471-2156-4-s1-s91	journal	January 2003
A Flexible and Accurate Genotype Imputation Method for the Next Generation of Genome-Wide Association Studies Howie, Bryan N.; Donnelly, Peter; Marchini, Jonathan PLoS Genetics, Vol. 5, Issue 6 https://doi.org/10.1371/journal.pgen.1000529	journal	June 2009

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