人类遗传学年鉴出版与人类遗传学或科学原理和技术在人类遗传任何方面的应用直接相关的材料。还将考虑描述可能与人类遗传学相关的其他物种的工作的论文。数学模型应尽可能包括数据应用示例。欢迎作者提交支持信息，例如数据集或其他图形或表格，这些信息不会在期刊的印刷版中发布，但可通过在线版本并存储在网站上。

The Annals of Human Genetics publishes research materials directly related to human genetics and the application of scientific principles and techniques in any aspect of human genetics. We also welcome papers describing work related to other species that may be relevant to human genetics. All mathematical models should include examples of data applications whenever possible. Authors are encouraged to submit supporting information, such as datasets or other graphics and tables, which will not be published in the print version of the journal but will be made available in the online version and stored on our website.

《Annals of Human Genetics》期刊出版与人类遗传学及其在各个领域的应用相关的研究材料。我们也欢迎与其他物种相关的研究论文，这些研究可能对人类遗传学有启发。所有数学模型应尽量包含数据应用的实例。我们鼓励作者提交支持性信息，例如数据集、图形或表格，这些信息将不会在期刊的印刷版中发布，但会在在线版本中提供，并存储在我们的网站上。

Annals of Human Genetics

Summary Mitochondrial aldehyde dehydrogenase (ALDH2) is one of the most important enzymes in human alcohol metabolism. The oriental ALDH2*504Lys variant functions as a dominant negative, greatly reducing activity in heterozygotes and abolishing activity in homozygotes. This allele is associated with serious disorders such as alcohol liver disease, late onset Alzheimer disease, colorectal cancer, and esophageal cancer, and is best known for protection against alcoholism. Many hundreds of papers in various languages have been published on this variant, providing allele frequency data for many different populations. To develop a highly refined global geographic distribution of ALDH2*504Lys , we have collected new data on 4,091 individuals from 86 population samples and assembled published data on a total of 80,691 individuals from 366 population samples. The allele is essentially absent in all parts of the world except East Asia. The ALDH2*504Lys allele has its highest frequency in Southeast China, and occurs in most areas of China, Japan, Korea, Mongolia, and Indochina with frequencies gradually declining radially from Southeast China. As the indigenous populations in South China have much lower frequencies than the southern Han migrants from Central China, we conclude that ALDH2*504Lys was carried by Han Chinese as they spread throughout East Asia. Esophageal cancer, with its highest incidence in East Asia, may be associated with ALDH2*504Lys because of a toxic effect of increased acetaldehyde in the tissue where ingested ethanol has its highest concentration. While the distributions of esophageal cancer and ALDH2*504Lys do not precisely correlate, that does not disprove the hypothesis. In general the study of fine scale geographic distributions of ALDH2*504Lys and diseases may help in understanding the multiple relationships among genes, diseases, environments, and cultures.

Hui Li

Svetlana Borinskaya

Kimio Yoshimura

Nina Kal’ina

Andrey Marusin

Vadim A. Stepanov

Zhendong Qin

Shagufta Khaliq

Mi‐Young Lee

Yajun Yang

Aisha Mohyuddin

David Gurwitz

Syed Qasim Mehdi

Evgeny Rogaev

Li Jin

Nikolay K. Yankovsky

Judith R. Kidd

Kenneth K. Kidd

Refined Geographic Distribution of the Oriental ALDH2*504Lys (nee 487Lys) Variant

东方ALDH2*504Lys（原名487Lys）变异体的精细地理分布

Summary A value S 2 , the sum of squares of deviations of the ten separate finger ridge‐counts from their mean, has been used as a measure of the diversity between the digits of an individual. Familial correlations have been estimated using a diversity index , the function (S/ √10), which is more symmetrically distributed than S 2 in a population sample (though the distribution is not Gaussian). Parent‐child, sib‐pair and dizygotic twin‐pair correlations are approximately 1/4, while the monozygotic twin correlation coefficient is 0–73 ± 0–06. It is concluded that the diversity of the ridge‐count from finger to finger has a genetic basis, but environmental influences during early pre‐natal development have a considerable effect. S 2 values for parents, children, additional sibs and twins are given in the Appendix. The data used for this paper are filed in the Archives at the Galton Laboratory.

SARAH B. HOLT

Genetics of dermal ridges: familial correlations for (S/√10), a measurement of the diversity of ridge‐counts from finger to finger

皮肤嵴遗传学：家族内 (S/√10) 的关联性分析，一种衡量手指间嵴数多样性的测量方法

Summary Deletions in the 9q33‐q34 region have been reported in patients with early onset epileptic encephalopathy, but a consistent phenotype has yet to emerge. We report on the diagnosis of a de novo 9q33‐q34.12 microdeletion of 4 Mb in a 15‐month‐old girl presenting with severe psychomotor delay, facial dysmorphisms, thin corpus callosum and early myoclonic encephalopathy. This deletion encompasses 101 RefSeq genes, including the four autosomal dominant genes STXBP1 , SPTAN1 , ENG and TOR1A . We discuss genetic, clinical and epileptic features comparing our patient with those previously reported in the literature.

Francesco Nicita

Fiorenza Ulgiati

Laura Bernardini

Giacomo Garone

Laura Papetti

Antonio Novelli

Alberto Spalice

Early Myoclonic Encephalopathy in 9q33‐q34 Deletion Encompassing STXBP1 and SPTAN1

9q33-q34 缺失包括 STXBP1 和 SPTAN1 的早期肌阵挛性脑病

ABSTRACT Introduction The common genetic underpinnings of psoriasis and pulmonary comorbidities have yet to be explored. Material and Methods In this cross‐sectional study, we investigated the single‐nucleotide polymorphisms (SNPs) associated with psoriasis and their relationship with pulmonary function using data from the UK Biobank (UKBB) and the Vanderbilt University Medical Center Biobank (BioVU). Results Out of the 63 psoriasis‐associated SNPs identified in previous genome‐wide association studies within the European population, we successfully identified 53 SNPs, including proxy SNPs in UKBB database. Following adjustments using age and sex, 31 SNPs displayed statistically significant associations with psoriasis. Among these, 16 SNPs exhibited significant associations with forced expiratory volume in 1 s (FEV 1 ), 14 with forced vital capacity (FVC), and 5 with the FEV 1 /FVC ratio in the UKBB. In the validation analysis using the BioVU database, 27 of the 31 psoriasis‐associated SNPs were available for examination. Notably, the minor allele of SNP rs8016947 was confirmed to be significant, indicating a reduced risk for psoriasis and improved FEV 1 . Similarly, the minor alleles of SNPs rs17716942 and rs8016947 were associated with a reduced risk of psoriasis and enhanced FVC. However, none of the 5 SNPs significantly associated with the FEV 1 /FVC ratio in the UKBB displayed significance in the BioVU dataset. Conclusion This study has unveiled genetic variants that bridge the realms of psoriasis and lung function. The genes associated with these variants, including IFIH1 , Grancalcin gene ( GCA ), and NFKB inhibitor alpha gene ( NFKBIA ), regulate innate immune responses, which suggests that immunodysregulation, a central element in psoriasis pathogenesis, may also impact lung function, alluding to a “skin–lung axis.”

Kazuya Tanimura

Melinda C. Aldrich

James Jaworski

Jinchuan Xing

Satoshi Okawa

Divay Chandra

Seyed M. Nouraie

Toru Nyunoya

Identifying a Genetic Link Between Lung Function and Psoriasis

识别肺功能与银屑病之间的遗传联系

Abstract Introduction Combined oxidative phosphorylation (OXPHOS) deficiency 44 (COXPD44; MIM# 618855) is caused by biallelic pathogenic variants in FAS‐activated serine–threonine kinase domain 2 ( FASTKD2) (MIM# 612322). COXPD44 is characterized by variable clinical features—developmental delay, chronic epileptic encephalopathy, seizure disorder/status epilepticus and cerebellar ataxia. We ascertained one sib with episodic acute encephalomyopathy triggered by acute gastroenteritis and associated with haematological abnormalities, rhabdomyolysis leading to acute kidney injury, hypotensive shock leading to early death and a similarly affected sib with early death. Both siblings were normal neurologically in between the acute episodes. Material and Methods Whole exome sequencing (WES) was performed in the elder sibling. Mitochondrial respiratory chain enzyme activity assaywas performed in fibroblast cells and muscle tissue of the elder sibling. Also, Adenosine triphosphate (ATP) determination assay was done in fibroblast cells of the elder sibling. Results WES revealed compound heterozygous missense likely pathogenic variants in FASTKD2 . Mitochondrial respiratory chain enzyme activity in muscle tissue showed reduced complex IV activity and ATP determination assay showed a reduction of ATP in skin fibroblasts. Conclusion Herein, we report two siblings with novel clinical phenotype associated with COXPD44. Our report further validates the biallelic variants in FASTKD2 associated with the variable phenotypes and mitochondrial OXPHOS defect.

Namanpreet Kaur

Puneeth H. Somashekar

Sekar Deepha

Periyasamy Govindaraj

Anju Shukla

Siddaramappa J. Patil

Intermittent episodes of acute severe encephalomyopathy and early death in two siblings caused by biallelic likely pathogenic variants in FASTKD2: Expanding phenotype and literature review

FASTKD2双等位基因可能致病变异导致两兄妹间歇性急性重度脑肌病及早期死亡：扩展表型及文献综述

Abstract Exome sequencing (ES) may identify and report secondary findings that are unrelated to the primary disease for which the patient underwent genetic testing, but are of potential value in patient care. In this study, we evaluated 81 American College of Medical Genetics (ACMG) medically actionable genes in 443 patients with various neurological disorders. The variants identified were classified and reported following the 2015 ACMG Standards and Guidelines for the interpretation of sequence variants and the ACMG recommendations for reporting secondary findings (v3.2). We detected a total of 17 variants in 17 patients across 9 different genes as secondary findings. Seven heterozygous variants were found in BRCA1, MSH2 , and PALB2 which are part of the cancer phenotype category. Nine heterozygous variants were found in MYH7 , TTN , LDLR , DSC2 , and DSP which are part of the cardiovascular phenotype category. Finally, one heterozygous variant was found in TTR which is part of the miscellaneous phenotype category. Thirteen of above mentioned variants were classified as known pathogenic and four as expected pathogenic. The information collected in our study may lead to the prevention of severe morbidity and mortality and provides additional insight into the genetic background of the Serbian population.

Marija Branković

Heonjong Han

Milena Janković

Ana Marjanović

Nikola Andrejic

Ilija Gunjić

Vanja Virić

Aleksa Palibrk

Hane Lee

Stojan Peric

Secondary findings in 443 exome sequencing data

443例全外显子测序数据的次要发现

Abstract Objective This study aims to investigate the potential causal relationship, shared genomic loci, as well as potential molecular pathways and tissue‐specific expression patterns between gastroesophageal reflux disease (GERD) and the risk of hospitalized/severe 2019 coronavirus disease (COVID‐19). Methods We employed linkage disequilibrium score regression and bidirectional Mendelian randomization (MR) analysis to explore potential genetic associations between GERD ( N = 602,604) and hospitalized COVID‐19 ( N = 2095,324) as well as severe COVID‐19 ( N = 1086,211). Additionally, shared genomic loci were extracted from common pivotal regions, further confirmed through corresponding colocalization analyses. GERD‐driven molecular pathway network was constructed using extensive literature data mining to understand the molecular‐level impacts of GERD on COVID‐19. Results Our results revealed a significant positive genetic correlation between GERD and both hospitalized ( r g = 0.418) and severe COVID‐19 ( r g = 0.314). Furthermore, the MR analysis demonstrated a unidirectional causal effect of genetic predisposition to GERD on COVID‐19 outcomes, including hospitalized COVID‐19 (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.27–1.44, p = 9.17e − 12) and severe COVID‐19 (OR: 1.27, 95% CI: 1.18–1.37, p = 1.20e − 05). Additionally, GERD and both COVID‐19 conditions shared one genomic locus with lead‐SNPs rs1011407 and rs1123573, corresponding to the transcription factor BCL11A. Colocalization analysis further demonstrated a significant positive correlation between genome‐wide association study and expression quantitative trait locus (eQTL) abnormalities, including rs1011407 (eQTL_ p = 2.35e − 07) and rs1123573 (eQTL_ p = 2.74e − 05). Molecular pathway analysis indicated that GERD might promote the progression of COVID‐19 by inducting immune‐activated and inflammation‐related pathways. Conclusion These findings confirm that genetically determined GERD may increase the susceptibility to hospitalized/severe COVID‐19. The shared genetic loci and the potential molecular pathways offer valuable insights into causal connections between GERD and COVID‐19.

Jingjing Pan

Jianhua Li

Gastroesophageal reflux disease increases predisposition to severe COVID‐19: Insights from integrated Mendelian randomization and genetic analysis

胃食管反流病增加重症新冠肺炎易感性：整合孟德尔随机化和遗传分析的见解

Abstract Introduction Activation‐induced cytidine deaminase (AID) deficiency is a rare autosomal recessive inborn error of immunity (IEI) characterized by increased susceptibility to infections, autoimmunity, and/or autoinflammation. AID plays an important role in immunoglobulin class switching and somatic hypermutation. AID deficiency patients have very low or absent levels of IgG, IgA, and IgE, while IgM level is elevated. The disease is designated as type 2 hyperimmunoglobulin M syndrome (HIGM‐2). To date, around 130 patients with HIGM‐2 have been reported, none from Egypt. Methods Four patients from three different consanguineous families with elevated serum IgM and low IgG and IgA were included in the study. After the exclusion of CD40 and/or CD40L deficiency by flow cytometry, patients’ samples were tested by a panel covering 452 genes (four bases PID‐Pro) on the Illumina Miseq platform. Results All patients suffered repeated infections since childhood. Patients 1–3 had inflammatory bowel disease‐like (IBD‐like) symptoms, while patient 4 did not have autoimmune manifestations. Patient 1 is the first HIGM‐2 patient to be reported to have renal amyloidosis as part of the autoinflammation. Patients 1–3 had the same pathogenic variant (NM_020661.4 ( AID ):c.406del, p.Ile136Ter), while patient 4 had another pathogenic variant (NM_020661.4 ( AID ):c.374G &gt; A, p.Gly125Glu). The variant p.Ile136Ter was not reported before in any of the documented HIGM‐2 patients. Conclusion HIGM‐2 is a rare IEI that can be overlooked; hence, patients’ diagnosis is delayed. Autoimmune and autoinflammatory manifestations develop later in the disease course leading to significant morbidities. The diagnosis can be suspected after exclusion of CD40/CD40L deficiencies by flow cytometry, and the diagnosis can be confirmed by genetic testing.

Safa S. Meshaal

Rabab E. El Hawary

Dalia S. Abd Elaziz

Alia Eldash

Rania Darwish

Aya Erfan

Sohilla Lotfy

Mai M. Saad

Engy A. Chohayeb

Mohamed S. Nagy

Radwa Alkady

Jeannette A. Boutros

Nermeen M. Galal

Aisha M. Elmarsafy

Clinical and immunological features of four patients with activation‐induced cytidine deaminase deficiency: Renal amyloidosis and other presentations

四例活化诱导的胞苷脱氨酶缺乏症患者的临床与免疫学特征：肾淀粉样变性及其他表现

Abbreviation	Ann. Hum. Genet.
Journal Impact	0.89
Quartiles(Global)	GENETICS & HEREDITY(Q4)

ISSN	0003-4800, 1469-1809
h-index	79

Publication Information	Publisher: Wiley-Blackwell Publishing Ltd，Publishing cycle: Bimonthly，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 1954，Proportion of original research papers: 92.86%，Self Citation Rate:0.00%， Gold OA Rate: 23.47%
Average review cycle	网友分享经验：平均6月
Average recruitment ratio	网友分享经验：约50%

Annals of Human Genetics

Journal Citation Format

A journal article with 1 author

A journal article with 2 authors

A journal article with 3 authors

A journal article with 5 or more authors

Books Citation Format

Thesis Citation Format

Web sites Citation Format

Patent Citation Format

Staying up late manually editing references? ivySCI automatically matches journals and helps you generate references with a single click.

Share Submission Experience

Refined Geographic Distribution of the Oriental ALDH2504Lys* (nee 487Lys) Variant

Genetics of dermal ridges: familial correlations for (S/√10), a measurement of the diversity of ridge‐counts from finger to finger

Early Myoclonic Encephalopathy in 9q33‐q34 Deletion Encompassing STXBP1 and SPTAN1

Identifying a Genetic Link Between Lung Function and Psoriasis

Intermittent episodes of acute severe encephalomyopathy and early death in two siblings caused by biallelic likely pathogenic variants in FASTKD2: Expanding phenotype and literature review

Identifying a Genetic Link Between Lung Function and Psoriasis

Intermittent episodes of acute severe encephalomyopathy and early death in two siblings caused by biallelic likely pathogenic variants in FASTKD2: Expanding phenotype and literature review

Secondary findings in 443 exome sequencing data

Gastroesophageal reflux disease increases predisposition to severe COVID‐19: Insights from integrated Mendelian randomization and genetic analysis

Clinical and immunological features of four patients with activation‐induced cytidine deaminase deficiency: Renal amyloidosis and other presentations