abstract：:We present a full-likelihood method to infer polygenic adaptation from DNA sequence variation and GWAS summary statistics to quantify recent transient directional selection acting on a complex trait. Through simulations of polygenic trait architecture evolution and GWASs, we show the method substantially improves powe...

journal_title：American journal of human genetics

authors： Stern AJ,Speidel L,Zaitlen NA,Nielsen R

更新日期：2021-01-08 00:00:00

abstract：:The genetics of African North Americans are complex amalgamations of various West and Central African peoples with modest gene flow from specific European and Amerindian peoples. A comprehensive understanding of African North American biohistory is a prerequisite for accurate interpretations of the ancestral genetics ...

journal_title：American journal of human genetics

authors： Jackson FLC

更新日期：2021-01-07 00:00:00

abstract：:Fibroblast growth factor homologous factors (FHFs) are intracellular proteins which regulate voltage-gated sodium (Nav) channels in the brain and other tissues. FHF dysfunction has been linked to neurological disorders including epilepsy. Here, we describe two sibling pairs and three unrelated males who presented in i...

journal_title：American journal of human genetics

authors： Fry AE,Marra C,Derrick AV,Pickrell WO,Higgins AT,Te Water Naude J,McClatchey MA,Davies SJ,Metcalfe KA,Tan HJ,Mohanraj R,Avula S,Williams D,Brady LI,Mesterman R,Tarnopolsky MA,Zhang Y,Yang Y,Wang X,Genomics England R

更新日期：2021-01-07 00:00:00

abstract：:Mastocytosis is a rare myeloid neoplasm characterized by uncontrolled expansion of mast cells, driven in >80% of affected individuals by acquisition of the KIT D816V mutation. To explore the hypothesis that inherited variation predisposes to mastocytosis, we performed a two-stage genome-wide association study, analyzi...

journal_title：American journal of human genetics

authors： Galatà G,García-Montero AC,Kristensen T,Dawoud AAZ,Muñoz-González JI,Meggendorfer M,Guglielmelli P,Hoade Y,Alvarez-Twose I,Gieger C,Strauch K,Ferrucci L,Tanaka T,Bandinelli S,Schnurr TM,Haferlach T,Broesby-Olsen S,Veste

更新日期：2021-01-04 00:00:00

abstract：:Genetic testing has increased the number of variants identified in disease genes, but the diagnostic utility is limited by lack of understanding variant function. CARD11 encodes an adaptor protein that expresses dominant-negative and gain-of-function variants associated with distinct immunodeficiencies. Here, we used ...

journal_title：American journal of human genetics

authors： Meitlis I,Allenspach EJ,Bauman BM,Phan IQ,Dabbah G,Schmitt EG,Camp ND,Torgerson TR,Nickerson DA,Bamshad MJ,Hagin D,Luthers CR,Stinson JR,Gray J,Lundgren I,Church JA,Butte MJ,Jordan MB,Aceves SS,Schwartz DM,Milner

更新日期：2020-12-03 00:00:00

abstract：:Plasma DNA fragmentomics is an emerging area in cell-free DNA diagnostics and research. In murine models, it has been shown that the extracellular DNase, DNASE1L3, plays a role in the fragmentation of plasma DNA. In humans, DNASE1L3 deficiency causes familial monogenic systemic lupus erythematosus with childhood onset...

journal_title：American journal of human genetics

authors： Chan RWY,Serpas L,Ni M,Volpi S,Hiraki LT,Tam LS,Rashidfarrokhi A,Wong PCH,Tam LHP,Wang Y,Jiang P,Cheng ASH,Peng W,Han DSC,Tse PPP,Lau PK,Lee WS,Magnasco A,Buti E,Sisirak V,AlMutairi N,Chan KCA,Chiu RWK,Reizi

更新日期：2020-11-05 00:00:00

abstract：:Human fetuses with trisomy 21 (T21) have atypical brain development that is apparent sonographically in the second trimester. We hypothesize that by analyzing and integrating dysregulated gene expression and pathways common to humans with Down syndrome (DS) and mouse models we can discover novel targets for prenatal t...

journal_title：American journal of human genetics

authors： Guedj F,Siegel AE,Pennings JLA,Alsebaa F,Massingham LJ,Tantravahi U,Bianchi DW

更新日期：2020-11-05 00:00:00

abstract：:Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and i...

journal_title：American journal of human genetics

authors： Thomas M,Sakoda LC,Hoffmeister M,Rosenthal EA,Lee JK,van Duijnhoven FJB,Platz EA,Wu AH,Dampier CH,de la Chapelle A,Wolk A,Joshi AD,Burnett-Hartman A,Gsur A,Lindblom A,Castells A,Win AK,Namjou B,Van Guelpen B,Tangen

更新日期：2020-09-03 00:00:00

abstract：:Secondary genomic findings are increasingly being returned to individuals as opportunistic screening results. A secondary finding offers the chance to identify and mitigate disease that may otherwise be unrecognized in an individual. As a form of screening, secondary findings must be considered differently from sequen...

journal_title：American journal of human genetics

authors： Katz AE,Nussbaum RL,Solomon BD,Rehm HL,Williams MS,Biesecker LG

更新日期：2020-07-02 00:00:00

abstract：:Sudden cardiac death is responsible for half of all deaths from cardiovascular disease. The analysis of the electrophysiological substrate for arrhythmias is crucial for optimal risk stratification. A prolonged T-peak-to-Tend (Tpe) interval on the electrocardiogram is an independent predictor of increased arrhythmic r...

journal_title：American journal of human genetics

authors： Ramírez J,van Duijvenboden S,Young WJ,Orini M,Lambiase PD,Munroe PB,Tinker A

更新日期：2020-06-04 00:00:00

abstract：:SOX6 belongs to a family of 20 SRY-related HMG-box-containing (SOX) genes that encode transcription factors controlling cell fate and differentiation in many developmental and adult processes. For SOX6, these processes include, but are not limited to, neurogenesis and skeletogenesis. Variants in half of the SOX genes ...

journal_title：American journal of human genetics

authors： Tolchin D,Yeager JP,Prasad P,Dorrani N,Russi AS,Martinez-Agosto JA,Haseeb A,Angelozzi M,Santen GWE,Ruivenkamp C,Mercimek-Andrews S,Depienne C,Kuechler A,Mikat B,Ludecke HJ,Bilan F,Le Guyader G,Gilbert-Dussardier B,Ker

更新日期：2020-06-04 00:00:00

abstract：:The Million Veteran Program (MVP), initiated by the Department of Veterans Affairs (VA), aims to collect biosamples with consent from at least one million veterans. Presently, blood samples have been collected from over 800,000 enrolled participants. The size and diversity of the MVP cohort, as well as the availabilit...

journal_title：American journal of human genetics

authors： Hunter-Zinck H,Shi Y,Li M,Gorman BR,Ji SG,Sun N,Webster T,Liem A,Hsieh P,Devineni P,Karnam P,Gong X,Radhakrishnan L,Schmidt J,Assimes TL,Huang J,Pan C,Humphries D,Brophy M,Moser J,Muralidhar S,Huang GD,Przygod

更新日期：2020-04-02 00:00:00

abstract：:Glycosylphosphatidylinositol (GPI)-anchored proteins are critical for embryogenesis, neurogenesis, and cell signaling. Variants in several genes participating in GPI biosynthesis and processing lead to decreased cell surface presence of GPI-anchored proteins (GPI-APs) and cause inherited GPI deficiency disorders (IGDs...

journal_title：American journal of human genetics

authors： Nguyen TTM,Murakami Y,Mobilio S,Niceta M,Zampino G,Philippe C,Moutton S,Zaki MS,James KN,Musaev D,Mu W,Baranano K,Nance JR,Rosenfeld JA,Braverman N,Ciolfi A,Millan F,Person RE,Bruel AL,Thauvin-Robinet C,Ververi A

更新日期：2020-04-02 00:00:00

abstract：:Recurrent somatic variants in SPOP are cancer specific; endometrial and prostate cancers result from gain-of-function and dominant-negative effects toward BET proteins, respectively. By using clinical exome sequencing, we identified six de novo pathogenic missense variants in SPOP in seven individuals with development...

journal_title：American journal of human genetics

authors： Nabais Sá MJ,El Tekle G,de Brouwer APM,Sawyer SL,Del Gaudio D,Parker MJ,Kanani F,van den Boogaard MH,van Gassen K,Van Allen MI,Wierenga K,Purcarin G,Elias ER,Begtrup A,Keller-Ramey J,Bernasocchi T,van de Wiel L,Gilissen

更新日期：2020-03-05 00:00:00

abstract：:Whether smoking-associated DNA methylation has a causal effect on lung function has not been thoroughly evaluated. We first investigated the causal effects of 474 smoking-associated CpGs on forced expiratory volume in 1 s (FEV1) in UK Biobank (n = 321,047) by using two-sample Mendelian randomization (MR) and then repl...

journal_title：American journal of human genetics

authors： Jamieson E,Korologou-Linden R,Wootton RE,Guyatt AL,Battram T,Burrows K,Gaunt TR,Tobin MD,Munafò M,Davey Smith G,Tilling K,Relton C,Richardson TG,Richmond RC

更新日期：2020-03-05 00:00:00

abstract：:Although quantitative trait locus (QTL) associations have been identified for many molecular traits such as gene expression, it remains challenging to distinguish the causal nucleotide from nearby variants. In addition to traditional QTLs by association, allele-specific (AS) QTLs are a powerful measure of cis-regulati...

journal_title：American journal of human genetics

authors： Wang AT,Shetty A,O'Connor E,Bell C,Pomerantz MM,Freedman ML,Gusev A

更新日期：2020-02-06 00:00:00

abstract：:Cytokines are essential regulatory components of the immune system, and their aberrant levels have been linked to many disease states. Despite increasing evidence that cytokines operate in concert, many of the physiological interactions between cytokines, and the shared genetic architecture that underlies them, remain...

journal_title：American journal of human genetics

authors： Nath AP,Ritchie SC,Grinberg NF,Tang HH,Huang QQ,Teo SM,Ahola-Olli AV,Würtz P,Havulinna AS,Santalahti K,Pitkänen N,Lehtimäki T,Kähönen M,Lyytikäinen LP,Raitoharju E,Seppälä I,Sarin AP,Ripatti S,Palotie A,Perola M,V

更新日期：2019-12-05 00:00:00

abstract：:Lissencephaly comprises a spectrum of malformations of cortical development. This spectrum includes agyria, pachygyria, and subcortical band heterotopia; each represents anatomical malformations of brain cortical development caused by neuronal migration defects. The molecular etiologies of neuronal migration anomalies...

journal_title：American journal of human genetics

authors： Mitani T,Punetha J,Akalin I,Pehlivan D,Dawidziuk M,Coban Akdemir Z,Yilmaz S,Aslan E,Hunter JV,Hijazi H,Grochowski CM,Jhangiani SN,Karaca E,Fatih JM,Iwanowski P,Gambin T,Wlasienko P,Goszczanska-Ciuchta A,Bekiesinska-Fi

更新日期：2019-11-07 00:00:00

abstract：:Aberrant gene expression underlies many human diseases. RNA polymerase II (Pol II) pausing is a key regulatory step in transcription. Here, we mapped the locations of RNA Pol II in normal human cells and found that RNA Pol II pauses in a consistent manner across individuals and cell types. At more than 1,000 genes inc...

journal_title：American journal of human genetics

authors： Watts JA,Burdick J,Daigneault J,Zhu Z,Grunseich C,Bruzel A,Cheung VG

更新日期：2019-10-03 00:00:00

abstract：:Neuroblastoma is a cancer of the developing sympathetic nervous system. It is diagnosed in 600-700 children per year in the United States and accounts for 12% of pediatric cancer deaths. Despite recent advances in our understanding of this malignancy's complex genetic architecture, the contribution of rare germline va...

journal_title：American journal of human genetics

authors： Egolf LE,Vaksman Z,Lopez G,Rokita JL,Modi A,Basta PV,Hakonarson H,Olshan AF,Diskin SJ

更新日期：2019-09-05 00:00:00

abstract：:The identification of genetic variants implicated in human developmental disorders has been revolutionized by second-generation sequencing combined with international pooling of cases. Here, we describe seven individuals who have diverse yet overlapping developmental anomalies, and who all have de novo missense FBXW11...

journal_title：American journal of human genetics

authors： Holt RJ,Young RM,Crespo B,Ceroni F,Curry CJ,Bellacchio E,Bax DA,Ciolfi A,Simon M,Fagerberg CR,van Binsbergen E,De Luca A,Memo L,Dobyns WB,Mohammed AA,Clokie SJH,Zazo Seco C,Jiang YH,Sørensen KP,Andersen H,Sullivan

更新日期：2019-09-05 00:00:00

abstract：:Histones mediate dynamic packaging of nuclear DNA in chromatin, a process that is precisely controlled to guarantee efficient compaction of the genome and proper chromosomal segregation during cell division and to accomplish DNA replication, transcription, and repair. Due to the important structural and regulatory rol...

journal_title：American journal of human genetics

authors： Flex E,Martinelli S,Van Dijck A,Ciolfi A,Cecchetti S,Coluzzi E,Pannone L,Andreoli C,Radio FC,Pizzi S,Carpentieri G,Bruselles A,Catanzaro G,Pedace L,Miele E,Carcarino E,Ge X,Chijiwa C,Lewis MES,Meuwissen M,Kenis S

更新日期：2019-09-05 00:00:00

abstract：:While genetic causes are known for many syndromes involving developmental anomalies, a large number of individuals with overlapping phenotypes remain undiagnosed. Using exome-sequencing analysis and review of matchmaker databases, we have discovered four de novo missense variants predicted to affect the N-terminal reg...

journal_title：American journal of human genetics

authors： Reis LM,Sorokina EA,Thompson S,Muheisen S,Velinov M,Zamora C,Aylsworth AS,Semina EV

更新日期：2019-08-01 00:00:00

abstract：:The Genes for Good study uses social media to engage a large, diverse participant pool in genetics research and education. Health history and daily tracking surveys are administered through a Facebook application, and participants who complete a minimum number of surveys are mailed a saliva sample kit ("spit kit") to ...

journal_title：American journal of human genetics

authors： Brieger K,Zajac GJM,Pandit A,Foerster JR,Li KW,Annis AC,Schmidt EM,Clark CP,McMorrow K,Zhou W,Yang J,Kwong AM,Boughton AP,Wu J,Scheller C,Parikh T,de la Vega A,Brazel DM,Frieser M,Rea-Sandin G,Fritsche LG,Vrieze

更新日期：2019-07-03 00:00:00

abstract：:Arthrogryposis is a clinical finding that is present either as a feature of a neuromuscular condition or as part of a systemic disease in over 400 Mendelian conditions. The underlying molecular etiology remains largely unknown because of genetic and phenotypic heterogeneity. We applied exome sequencing (ES) in a cohor...

journal_title：American journal of human genetics

authors： Pehlivan D,Bayram Y,Gunes N,Coban Akdemir Z,Shukla A,Bierhals T,Tabakci B,Sahin Y,Gezdirici A,Fatih JM,Gulec EY,Yesil G,Punetha J,Ocak Z,Grochowski CM,Karaca E,Albayrak HM,Radhakrishnan P,Erdem HB,Sahin I,Yildirim

更新日期：2019-07-03 00:00:00

abstract：:The heterogeneous nuclear ribonucleoprotein (HNRNP) genes code for a set of RNA-binding proteins that function primarily in the spliceosome C complex. Pathogenic variants in these genes can drive neurodegeneration, through a mechanism involving excessive stress-granule formation, or developmental defects, through mech...

journal_title：American journal of human genetics

authors： Duijkers FA,McDonald A,Janssens GE,Lezzerini M,Jongejan A,van Koningsbruggen S,Leeuwenburgh-Pronk WG,Wlodarski MW,Moutton S,Tran-Mau-Them F,Thauvin-Robinet C,Faivre L,Monaghan KG,Smol T,Boute-Benejean O,Ladda RL,Sell SL,

更新日期：2019-06-06 00:00:00

abstract：:Understanding the nature of the genetic regulation of gene expression promises to advance our understanding of the genetic basis of disease. However, the methodological impact of the use of local ancestry on high-dimensional omics analyses, including, most prominently, expression quantitative trait loci (eQTL) mapping...

journal_title：American journal of human genetics

authors： Zhong Y,Perera MA,Gamazon ER

更新日期：2019-06-06 00:00:00

abstract：:Holoprosencephaly is the incomplete separation of the forebrain during embryogenesis. Both genetic and environmental etiologies have been determined for holoprosencephaly; however, a genetic etiology is not found in most cases. In this report, we present two unrelated individuals with semilobar holoprosencephaly who h...

journal_title：American journal of human genetics

authors： Kruszka P,Berger SI,Weiss K,Everson JL,Martinez AF,Hong S,Anyane-Yeboa K,Lipinski RJ,Muenke M

更新日期：2019-05-02 00:00:00

abstract：:Whole-genome sequencing (WGS) studies are being widely conducted in order to identify rare variants associated with human diseases and disease-related traits. Classical single-marker association analyses for rare variants have limited power, and variant-set-based analyses are commonly used by researchers for analyzing...

journal_title：American journal of human genetics

authors： Li Z,Li X,Liu Y,Shen J,Chen H,Zhou H,Morrison AC,Boerwinkle E,Lin X

更新日期：2019-05-02 00:00:00

abstract：:Mutations in several genes encoding components of the SWI/SNF chromatin remodeling complex cause neurodevelopmental disorders (NDDs). Here, we report on five individuals with mutations in SMARCD1; the individuals present with developmental delay, intellectual disability, hypotonia, feeding difficulties, and small hand...

journal_title：American journal of human genetics

authors： Nixon KCJ,Rousseau J,Stone MH,Sarikahya M,Ehresmann S,Mizuno S,Matsumoto N,Miyake N,DDD Study.,Baralle D,McKee S,Izumi K,Ritter AL,Heide S,Héron D,Depienne C,Titheradge H,Kramer JM,Campeau PM

更新日期：2019-04-04 00:00:00

abstract：:Ciliopathies are clinical disorders of the primary cilium with widely recognized phenotypic and genetic heterogeneity. In two Arab consanguineous families, we mapped a ciliopathy phenotype that most closely matches Joubert syndrome (hypotonia, developmental delay, typical facies, oculomotor apraxia, polydactyly, and s...

journal_title：American journal of human genetics

authors： Shaheen R,Jiang N,Alzahrani F,Ewida N,Al-Sheddi T,Alobeid E,Musaev D,Stanley V,Hashem M,Ibrahim N,Abdulwahab F,Alshenqiti A,Sonmez FM,Saqati N,Alzaidan H,Al-Qattan MM,Al-Mohanna F,Gleeson JG,Alkuraya FS

更新日期：2019-04-04 00:00:00

abstract：:Although the use of model systems for studying the mechanism of mutations that have a large effect is common, we highlight here the ways that zebrafish-model-system studies of a gene, GRIK5, that contributes to the polygenic liability to develop eye diseases have helped to illuminate a mechanism that implicates vascul...

journal_title：American journal of human genetics

authors： Unlu G,Gamazon ER,Qi X,Levic DS,Bastarache L,Denny JC,Roden DM,Mayzus I,Breyer M,Zhong X,Konkashbaev AI,Rzhetsky A,Knapik EW,Cox NJ

更新日期：2019-03-07 00:00:00

abstract：:Each year at the annual meeting of The American Society of Human Genetics (ASHG), addresses are given in honor of the Society and a number of award winners. A summary of each of these is provided below. On the following pages, we have printed the Presidential Address as well as the addresses for the William Allan Awar...

journal_title：American journal of human genetics

authors：

更新日期：2019-03-07 00:00:00

abstract：:Personalized genetic information is not widely utilized as a resource in learning environments, in part because of concerns about data privacy and the treatment of sensitive personal information. Here we describe the implementation of a curriculum centered on analyzing personalized genetic-ancestry test results during...

journal_title：American journal of human genetics

authors： Wright EA,Wagner JK,Shriver MD,Fernandez JR,Jablonski NG

更新日期：2019-02-07 00:00:00

abstract：:Steroid-resistant nephrotic syndrome (SRNS) is characterized by high-range proteinuria and most often focal and segmental glomerulosclerosis (FSGS). Identification of mutations in genes causing SRNS has improved our understanding of disease mechanisms and highlighted defects in the podocyte, a highly specialized glome...

journal_title：American journal of human genetics

authors： Dorval G,Kuzmuk V,Gribouval O,Welsh GI,Bierzynska A,Schmitt A,Miserey-Lenkei S,Koziell A,Haq S,Benmerah A,Mollet G,Boyer O,Saleem MA,Antignac C

更新日期：2019-02-07 00:00:00

abstract：:Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to e...

journal_title：American journal of human genetics

authors： Mavaddat N,Michailidou K,Dennis J,Lush M,Fachal L,Lee A,Tyrer JP,Chen TH,Wang Q,Bolla MK,Yang X,Adank MA,Ahearn T,Aittomäki K,Allen J,Andrulis IL,Anton-Culver H,Antonenkova NN,Arndt V,Aronson KJ,Auer PL,Auvinen

更新日期：2019-01-03 00:00:00

abstract：:Functional genomics data has the potential to increase GWAS power by identifying SNPs that have a higher prior probability of association. Here, we introduce a method that leverages polygenic functional enrichment to incorporate coding, conserved, regulatory, and LD-related genomic annotations into association analyse...

journal_title：American journal of human genetics

authors： Kichaev G,Bhatia G,Loh PR,Gazal S,Burch K,Freund MK,Schoech A,Pasaniuc B,Price AL

更新日期：2019-01-03 00:00:00

abstract：:The use of whole-exome and whole-genome sequencing has been a catalyst for a genotype-first approach to diagnostics. Under this paradigm, we have implemented systematic sequencing of neonates and young children with a suspected genetic disorder. Here, we report on two families with recessive mutations in NCAPG2 and ov...

journal_title：American journal of human genetics

authors： Khan TN,Khan K,Sadeghpour A,Reynolds H,Perilla Y,McDonald MT,Gallentine WB,Baig SM,Task Force for Neonatal Genomics.,Davis EE,Katsanis N

更新日期：2019-01-03 00:00:00

abstract：:RNA sequencing (RNA-seq) is gaining popularity as a complementary assay to genome sequencing for precisely identifying the molecular causes of rare disorders. A powerful approach is to identify aberrant gene expression levels as potential pathogenic events. However, existing methods for detecting aberrant read counts ...

journal_title：American journal of human genetics

authors： Brechtmann F,Mertes C,Matusevičiūtė A,Yépez VA,Avsec Ž,Herzog M,Bader DM,Prokisch H,Gagneur J

更新日期：2018-12-06 00:00:00

abstract：:Ca2+ signaling is vital for various cellular processes including synaptic vesicle exocytosis, muscle contraction, regulation of secretion, gene transcription, and cellular proliferation. The endoplasmic reticulum (ER) is the largest intracellular Ca2+ store, and dysregulation of ER Ca2+ signaling and homeostasis contr...

journal_title：American journal of human genetics

authors： Morimoto M,Waller-Evans H,Ammous Z,Song X,Strauss KA,Pehlivan D,Gonzaga-Jauregui C,Puffenberger EG,Holst CR,Karaca E,Brigatti KW,Maguire E,Coban-Akdemir ZH,Amagata A,Lau CC,Chepa-Lotrea X,Macnamara E,Tos T,Isikay S,

更新日期：2018-11-01 00:00:00