Broad and narrow heritabilities of quantitative traits in a founder population.

Abstract:

:Estimation of the components of variance for a quantitative trait allows one to evaluate both the degree to which genetics influences the trait and the trait's underlying genetic architecture. For particular traits, the estimates also may have implications for discriminating between potential models of selection and for choosing an appropriate model for linkage analysis. Using a recently developed method, we estimate the additive and dominance components of variance--or, equivalently, the narrow and broad sense heritabilities--of several traits in the Hutterites, a founder population with extensive genealogical records. As a result of inbreeding and because Hutterite individuals are typically related through multiple lines of descent, we expect that power to detect dominance variance will be increased relative to that in outbred studies. Furthermore, the communal lifestyle of the Hutterites allows us to evaluate the genetic influences in a relatively homogeneous environment. Four phenotypes had a significant dominance variance, resulting in a relatively high broad heritability. We estimated the narrow and broad heritabilities as being, respectively,.36 and.96 for LDL,.51 and 1.0 for serotonin levels, and.45 and.76 for fat free mass (FFM). There was no significant additive component for systolic blood pressure (SBP), resulting in a narrow heritability of 0 and a broad heritability of.45. There were several traits for which we found no significant dominance component, resulting in equal broad and narrow heritability estimates. These traits and their heritabilities are as follows: HDL,.63; triglycerides,.37; diastolic blood pressure,.21; immunoglobulin E,.63; lipoprotein(a),.77; and body-mass index,.54. The large difference between broad and narrow heritabilities for LDL, serotonin, FFM, and SBP are indicative of strong dominance effects in these phenotypes. To our knowledge, this is the first study to report an estimate of heritability for serotonin and to detect a dominance variance for LDL, FFM, and SBP.

journal_name

Am J Hum Genet

authors

Abney M,McPeek MS,Ober C

doi

10.1086/320112

subject

Has Abstract

pub_date

2001-05-01 00:00:00

pages

1302-7

issue

5

eissn

0002-9297

issn

1537-6605

pii

S0002-9297(07)61241-5

journal_volume

68

pub_type

杂志文章
  • The molecular basis of X-linked spondyloepiphyseal dysplasia tarda.

    abstract::The X-linked form of spondyloepiphyseal dysplasia tarda (SEDL), a radiologically distinct skeletal dysplasia affecting the vertebrae and epiphyses, is caused by mutations in the SEDL gene. To characterize the molecular basis for SEDL, we have identified the spectrum of SEDL mutations in 30 of 36 unrelated cases of X-l...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:10.1086/320592

    authors: Gedeon AK,Tiller GE,Le Merrer M,Heuertz S,Tranebjaerg L,Chitayat D,Robertson S,Glass IA,Savarirayan R,Cole WG,Rimoin DL,Kousseff BG,Ohashi H,Zabel B,Munnich A,Gecz J,Mulley JC

    更新日期:2001-06-01 00:00:00

  • Truncating Variants in NAA15 Are Associated with Variable Levels of Intellectual Disability, Autism Spectrum Disorder, and Congenital Anomalies.

    abstract::N-alpha-acetylation is a common co-translational protein modification that is essential for normal cell function in humans. We previously identified the genetic basis of an X-linked infantile lethal Mendelian disorder involving a c.109T>C (p.Ser37Pro) missense variant in NAA10, which encodes the catalytic subunit of t...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:10.1016/j.ajhg.2018.03.004

    authors: Cheng H,Dharmadhikari AV,Varland S,Ma N,Domingo D,Kleyner R,Rope AF,Yoon M,Stray-Pedersen A,Posey JE,Crews SR,Eldomery MK,Akdemir ZC,Lewis AM,Sutton VR,Rosenfeld JA,Conboy E,Agre K,Xia F,Walkiewicz M,Longoni M,H

    更新日期:2018-05-03 00:00:00

  • Multipoint interval mapping of quantitative trait loci, using sib pairs.

    abstract::The sib-pair interval-mapping procedure of Fulker and Cardon is extended to take account of all available marker information on a chromosome simultaneously. The method provides a computationally fast multipoint analysis of sib-pair data, using a modified Haseman-Elston approach. It gives results very similar to those ...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:

    authors: Fulker DW,Cherny SS,Cardon LR

    更新日期:1995-05-01 00:00:00

  • Evidence that paternal expression of the epsilon-sarcoglycan gene accounts for reduced penetrance in myoclonus-dystonia.

    abstract::Myoclonus-dystonia (M-D) is a movement disorder characterized by rapid muscle contractions and sustained twisting and repetitive movements and has recently been associated with mutations in the epsilon-sarcoglycan gene (SGCE). The mode of inheritance is autosomal dominant with reduced penetrance upon maternal transmis...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:10.1086/344531

    authors: Müller B,Hedrich K,Kock N,Dragasevic N,Svetel M,Garrels J,Landt O,Nitschke M,Pramstaller PP,Reik W,Schwinger E,Sperner J,Ozelius L,Kostic V,Klein C

    更新日期:2002-12-01 00:00:00

  • Evidence for recessive and against dominant inheritance at the HLA-"linked" locus in coeliac disease.

    abstract::It has been proposed that gluten sensitive enteropathy (GSE) results from the interaction of two loci: one locus linked to HLA and associated with dominant inheritance, and the other, a non-HLA-linked GSE-associated B-cell alloantigen, exhibiting recessive inheritance. We have shown in previous analyses that a two-loc...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:

    authors: Greenberg DA,Hodge SE,Rotter JI

    更新日期:1982-03-01 00:00:00

  • Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1.

    abstract::Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10(-5)) in 2871 additional cases and ...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:10.1016/j.ajhg.2011.10.002

    authors: Bown MJ,Jones GT,Harrison SC,Wright BJ,Bumpstead S,Baas AF,Gretarsdottir S,Badger SA,Bradley DT,Burnand K,Child AH,Clough RE,Cockerill G,Hafez H,Scott DJ,Futers S,Johnson A,Sohrabi S,Smith A,Thompson MM,van Bockxm

    更新日期:2011-11-11 00:00:00

  • Genetic analysis of plasma sitosterol, apoprotein B, and lipoproteins in a large Amish pedigree with sitosterolemia.

    abstract::We previously reported the finding of phytosterolemia, xanthomatosis, and hyperapobetalipoproteinemia (hyperapoB) in five siblings in a large Amish pedigree ascertained through a 13-year-old boy who died suddenly from advanced coronary atherosclerosis. Here, we present further analyses of the plasma levels of the plan...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:

    authors: Beaty TH,Kwiterovich PO Jr,Khoury MJ,White S,Bachorik PS,Smith HH,Teng B,Sniderman A

    更新日期:1986-04-01 00:00:00

  • A higher mutational burden in females supports a "female protective model" in neurodevelopmental disorders.

    abstract::Increased male prevalence has been repeatedly reported in several neurodevelopmental disorders (NDs), leading to the concept of a "female protective model." We investigated the molecular basis of this sex-based difference in liability and demonstrated an excess of deleterious autosomal copy-number variants (CNVs) in f...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:10.1016/j.ajhg.2014.02.001

    authors: Jacquemont S,Coe BP,Hersch M,Duyzend MH,Krumm N,Bergmann S,Beckmann JS,Rosenfeld JA,Eichler EE

    更新日期:2014-03-06 00:00:00

  • Identification of two cosmids derived from within chromosomal band 3p21.1 that contain clusters of rare restriction sites and evolutionarily conserved sequences.

    abstract::We have isolated large numbers of human recombinants from a cosmid library constructed from an interspecific (hamster/human) somatic cell hybrid whose only human component is an intact chromosome 3. Unique sequence probes were isolated from these recombinants and were used to localize them along the length of chromoso...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:

    authors: Smith DI,Golembieski W,Drabkin H,Kiousis S

    更新日期:1989-09-01 00:00:00

  • Gaucher disease: gene frequencies in the Ashkenazi Jewish population.

    abstract::DNA from over 2,000 Ashkenazi Jewish subjects has been examined for the four most common Jewish Gaucher disease mutations, which collectively account for about 96% of the disease-producing alleles in Jewish patients. This population survey has made possible the estimation of gene frequencies for these alleles. Eighty-...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:

    authors: Beutler E,Nguyen NJ,Henneberger MW,Smolec JM,McPherson RA,West C,Gelbart T

    更新日期:1993-01-01 00:00:00

  • Submicroscopic deletions at the WAGR locus, revealed by nonradioactive in situ hybridization.

    abstract::Fluorescence in situ hybridization (FISH) with biotin-labeled probes mapping to 11p13 has been used for the molecular analysis of deletions of the WAGR (Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation) locus. We have detected a submicroscopic 11p13 deletion in a child with inherited aniridia...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:

    authors: Fantes JA,Bickmore WA,Fletcher JM,Ballesta F,Hanson IM,van Heyningen V

    更新日期:1992-12-01 00:00:00

  • An evaluation of three statistics of structured exploratory data analysis.

    abstract::The power of structured exploratory data analysis (SEDA) to discriminate among major genic, polygenic, and nongenetic determination of phenotypes was investigated using computer simulation. Three classes of SEDA indices (the major gene index, the offspring between parents function, and the midparent-child correlation ...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:

    authors: Kammerer CM,MacCluer JW,Bridges JM

    更新日期:1984-01-01 00:00:00

  • Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations.

    abstract::Alcoholism is a complex disease with both genetic and environmental risk factors. To identify genes that affect the risk for alcoholism, we systematically ascertained and carefully assessed individuals in families with multiple alcoholics. Linkage and association analyses suggested that a region of chromosome 4p conta...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:10.1086/383283

    authors: Edenberg HJ,Dick DM,Xuei X,Tian H,Almasy L,Bauer LO,Crowe RR,Goate A,Hesselbrock V,Jones K,Kwon J,Li TK,Nurnberger JI Jr,O'Connor SJ,Reich T,Rice J,Schuckit MA,Porjesz B,Foroud T,Begleiter H

    更新日期:2004-04-01 00:00:00

  • Branching enzyme activity of cultured amniocytes and chorionic villi: prenatal testing for type IV glycogen storage disease.

    abstract::Although type IV glycogen storage disease (Andersen disease; McKusick 23250) is considered to be a rare, autosomally recessive disorder, of the more than 600 patients with glycogenosis identified in our laboratory by enzymatic assays, 6% have been shown to be deficient in the glycogen branching enzyme. Most of the 38 ...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:

    authors: Brown BI,Brown DH

    更新日期:1989-03-01 00:00:00

  • A 3-bp deletion in the rhodopsin gene in a family with autosomal dominant retinitis pigmentosa.

    abstract::Autosomal dominant retinitis pigmentosa (ADRP) has recently been linked to locus D3S47 (probe C17), with no recombination, in a single large Irish family. Other ADRP pedigrees have shown linkage at zero recombination, linkage with recombination, and no linkage, demonstrating genetic heterogeneity. The gene encoding rh...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:

    authors: Inglehearn CF,Bashir R,Lester DH,Jay M,Bird AC,Bhattacharya SS

    更新日期:1991-01-01 00:00:00

  • Linkage analysis of human leukocyte antigen (HLA) markers in familial psoriasis: strong disequilibrium effects provide evidence for a major determinant in the HLA-B/-C region.

    abstract::Although psoriasis is strongly associated with certain human leukocyte antigens (HLAs), evidence for linkage to HLA markers has been limited. The objectives of this study were (1) to provide more definitive evidence for linkage of psoriasis to HLA markers in multiplex families; (2) to compare the major HLA risk allele...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:10.1086/301899

    authors: Jenisch S,Henseler T,Nair RP,Guo SW,Westphal E,Stuart P,Krönke M,Voorhees JJ,Christophers E,Elder JT

    更新日期:1998-07-01 00:00:00

  • Linkage analysis of the apolipoprotein C2 gene and myotonic dystrophy on human chromosome 19 reveals linkage disequilibrium in a French-Canadian population.

    abstract::The gene for human apolipoprotein C2 (APOC2), situated on the proximal long arm of chromosome 19, is closely linked to the gene for the most common form of adult muscular dystrophy, myotonic dystrophy (DM). Six APOC2 RFLPs (TaqI, BglI, BanI, BamHI, NcoI, and AvaII) have been identified to date. We have conducted a com...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:

    authors: MacKenzie AE,MacLeod HL,Hunter AG,Korneluk RG

    更新日期:1989-01-01 00:00:00

  • Genetic linkage of attention-deficit/hyperactivity disorder on chromosome 16p13, in a region implicated in autism.

    abstract::Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed behavioral disorder in childhood and likely represents an extreme of normal behavior. ADHD significantly impacts learning in school-age children and leads to impaired functioning throughout the life span. There is strong evidence for a gene...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:10.1086/342732

    authors: Smalley SL,Kustanovich V,Minassian SL,Stone JL,Ogdie MN,McGough JJ,McCracken JT,MacPhie IL,Francks C,Fisher SE,Cantor RM,Monaco AP,Nelson SF

    更新日期:2002-10-01 00:00:00

  • Model-free linkage analysis using likelihoods.

    abstract::Misspecification of transmission model parameters can produce artifactually negative lod scores at small recombination fractions and in multipoint analysis. To avoid this problem, we have tried to devise a test that aims to detect a genetic effect at a particular locus, rather than attempting to estimate the map posit...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:

    authors: Curtis D,Sham PC

    更新日期:1995-09-01 00:00:00

  • Next-generation sequencing reveals deep intronic cryptic ABCC8 and HADH splicing founder mutations causing hyperinsulinism by pseudoexon activation.

    abstract::Next-generation sequencing (NGS) enables analysis of the human genome on a scale previously unachievable by Sanger sequencing. Exome sequencing of the coding regions and conserved splice sites has been very successful in the identification of disease-causing mutations, and targeting of these regions has extended clini...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:10.1016/j.ajhg.2012.11.017

    authors: Flanagan SE,Xie W,Caswell R,Damhuis A,Vianey-Saban C,Akcay T,Darendeliler F,Bas F,Guven A,Siklar Z,Ocal G,Berberoglu M,Murphy N,O'Sullivan M,Green A,Clayton PE,Banerjee I,Clayton PT,Hussain K,Weedon MN,Ellard S

    更新日期:2013-01-10 00:00:00

  • The mutational spectrum in Treacher Collins syndrome reveals a predominance of mutations that create a premature-termination codon.

    abstract::Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate. The TCS locus has been mapped to human chromosome 5q31.3-32 and the mutated gene identified. In the current investigation, 25 previously undescribed mut...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:

    authors: Edwards SJ,Gladwin AJ,Dixon MJ

    更新日期:1997-03-01 00:00:00

  • A truncating mutation in SERPINB6 is associated with autosomal-recessive nonsyndromic sensorineural hearing loss.

    abstract::More than 270 million people worldwide have hearing loss that affects normal communication. Although astonishing progress has been made in the identification of more than 50 genes for deafness during the past decade, the majority of deafness genes are yet to be identified. In this study, we mapped a previously unknown...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:10.1016/j.ajhg.2010.04.004

    authors: Sirmaci A,Erbek S,Price J,Huang M,Duman D,Cengiz FB,Bademci G,Tokgöz-Yilmaz S,Hişmi B,Ozdağ H,Oztürk B,Kulaksizoğlu S,Yildirim E,Kokotas H,Grigoriadou M,Petersen MB,Shahin H,Kanaan M,King MC,Chen ZY,Blanton SH,L

    更新日期:2010-05-14 00:00:00

  • Genomewide linkage scan identifies a novel susceptibility locus for restless legs syndrome on chromosome 9p.

    abstract::Restless legs syndrome (RLS) is a common neurological disorder that affects 5%-12% of all whites. To genetically dissect this complex disease, we characterized 15 large and extended multiplex pedigrees, consisting of 453 subjects (134 affected with RLS). A familial aggregation analysis was performed, and SAGE FCOR was...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:10.1086/420772

    authors: Chen S,Ondo WG,Rao S,Li L,Chen Q,Wang Q

    更新日期:2004-05-01 00:00:00

  • Determinants of exon 7 splicing in the spinal muscular atrophy genes, SMN1 and SMN2.

    abstract::Spinal muscular atrophy is a neurodegenerative disorder caused by the deletion or mutation of the survival-of-motor-neuron gene, SMN1. An SMN1 paralog, SMN2, differs by a C-->T transition in exon 7 that causes substantial skipping of this exon, such that SMN2 expresses only low levels of functional protein. A better u...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:10.1086/498853

    authors: Cartegni L,Hastings ML,Calarco JA,de Stanchina E,Krainer AR

    更新日期:2006-01-01 00:00:00

  • Lack of homozygotes for the most frequent disease allele in carbohydrate-deficient glycoprotein syndrome type 1A.

    abstract::Carbohydrate-deficient-glycoprotein syndrome type 1 (CDG1; also known as "Jaeken syndrome") is an autosomal recessive disorder characterized by defective glycosylation. Most patients show a deficiency of phosphomannomutase (PMM), the enzyme that converts mannose 6-phosphate to mannose 1-phosphate in the synthesis of G...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:10.1086/301763

    authors: Matthijs G,Schollen E,Van Schaftingen E,Cassiman JJ,Jaeken J

    更新日期:1998-03-01 00:00:00

  • Deletion of the entire cytochrome P450 CYP2D6 gene as a cause of impaired drug metabolism in poor metabolizers of the debrisoquine/sparteine polymorphism.

    abstract::The debrisoquine/sparteine polymorphism is associated with a clinically important genetic deficiency of oxidative drug metabolism. From 5% to 10% of Caucasians designated as poor metabolizers (PMs) of the debrisoquine/sparteine polymorphism have a severely impaired capacity to metabolize more than 25 therapeutically u...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:

    authors: Gaedigk A,Blum M,Gaedigk R,Eichelbaum M,Meyer UA

    更新日期:1991-05-01 00:00:00

  • Multiple independent molecular etiology for limb-girdle muscular dystrophy type 2A patients from various geographical origins.

    abstract::Limb-girdle muscular dystrophies (LGMDs) are a group of neuromuscular diseases presenting great clinical heterogeneity. Mutations in CANP3, the gene encoding muscle-specific calpain, were used to identify this gene as the genetic site responsible for autosomal recessive LGMD type 2A (LGMD2A; MIM 253600). Analyses of t...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:

    authors: Richard I,Brenguier L,Dinçer P,Roudaut C,Bady B,Burgunder JM,Chemaly R,Garcia CA,Halaby G,Jackson CE,Kurnit DM,Lefranc G,Legum C,Loiselet J,Merlini L,Nivelon-Chevallier A,Ollagnon-Roman E,Restagno G,Topaloglu H,Beck

    更新日期:1997-05-01 00:00:00

  • Autosomal dominant orthostatic hypotensive disorder maps to chromosome 18q.

    abstract::Familial orthostatic hypotensive disorder is characterized by light-headedness on standing, which may worsen to syncope, palpitations, and blue-purple ankle discoloration, and is accompanied by a marked decrease in systolic blood pressure, an increase in diastolic pressure, and tachycardia, all of which resolve when s...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:10.1086/302096

    authors: DeStefano AL,Baldwin CT,Burzstyn M,Gavras I,Handy DE,Joost O,Martel T,Nicolaou M,Schwartz F,Streeten DH,Farrer LA,Gavras H

    更新日期:1998-11-01 00:00:00

  • Neurological phenotype in Waardenburg syndrome type 4 correlates with novel SOX10 truncating mutations and expression in developing brain.

    abstract::Waardenburg syndrome type 4 (WS4), also called Shah-Waardenburg syndrome, is a rare neurocristopathy that results from the absence of melanocytes and intrinsic ganglion cells of the terminal hindgut. WS4 is inherited as an autosomal recessive trait attributable to EDN3 or EDNRB mutations. It is inherited as an autosom...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:10.1086/302895

    authors: Touraine RL,Attié-Bitach T,Manceau E,Korsch E,Sarda P,Pingault V,Encha-Razavi F,Pelet A,Augé J,Nivelon-Chevallier A,Holschneider AM,Munnes M,Doerfler W,Goossens M,Munnich A,Vekemans M,Lyonnet S

    更新日期:2000-05-01 00:00:00

  • Mitotic Intragenic Recombination: A Mechanism of Survival for Several Congenital Disorders of Glycosylation.

    abstract::Congenital disorders of glycosylation (CDGs) are disorders of abnormal protein glycosylation that affect multiple organ systems. Because most CDGs have been described in only a few individuals, our understanding of the associated phenotypes and the mechanisms of individual survival are limited. In the process of study...

    journal_title:American journal of human genetics

    pub_type: 杂志文章

    doi:10.1016/j.ajhg.2015.12.007

    authors: Kane MS,Davids M,Adams C,Wolfe LA,Cheung HW,Gropman A,Huang Y,NISC Comparative Sequencing Program.,Ng BG,Freeze HH,Adams DR,Gahl WA,Boerkoel CF

    更新日期:2016-02-04 00:00:00