Journal of Human Genetics最新文献_第2页

Development of a method for the imputation of the multi-allelic serotonin-transporter-linked polymorphic region (5-HTTLPR) in the Japanese population. 开发日本人口中与血清素-转运体相关的多态性区域（5-HTTLPR）的多等位基因估算方法。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-09-25 DOI: 10.1038/s10038-024-01296-9

Yutaro Yanagida, Izumi Naka, Yutaka Nakachi, Tempei Ikegame, Kiyoto Kasai, Naoto Kajitani, Minoru Takebayashi, Miki Bundo, Jun Ohashi, Kazuya Iwamoto

{"title":"Development of a method for the imputation of the multi-allelic serotonin-transporter-linked polymorphic region (5-HTTLPR) in the Japanese population.","authors":"Yutaro Yanagida, Izumi Naka, Yutaka Nakachi, Tempei Ikegame, Kiyoto Kasai, Naoto Kajitani, Minoru Takebayashi, Miki Bundo, Jun Ohashi, Kazuya Iwamoto","doi":"10.1038/s10038-024-01296-9","DOIUrl":"https://doi.org/10.1038/s10038-024-01296-9","url":null,"abstract":"Serotonin-transporter-linked polymorphic region (5-HTTLPR), a variable number of tandem repeats in the promoter region of serotonin transporter gene, is classified into short (S) and long (L) alleles. Initial case-control association studies claiming the risks of the S allele in depression and anxiety were not completely supported by recent studies. However, most studies, especially those on East Asian populations, have overlooked the complexity of 5-HTTLPR, which involves multiple different alleles with distinct functional properties. To address this issue, distinguishing multiple 5-HTTLPR alleles is essential. Here, using the 5-HTTLPR genotypes previously determined by exhaustive Sanger sequencing of approximately 1,500 Japanese subjects and their comprehensive SNP data, we constructed a method for 5-HTTLPR genotype imputation. We identified 28 tag SNPs for the imputation of four major 5-HTTLPR alleles, which collectively account for 97.6% of 5-HTTLPR alleles in the Japanese population. Our imputation method, achieved an accuracy of 0.872 in cross-validation, will contribute to association analysis of 5-HTTLPR in the Japanese subjects.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: Association study of GBA1 variants with MSA based on comprehensive sequence analysis -Pitfalls in short-read sequence analysis depending on the human reference genome. 更正：基于综合序列分析的GBA1变异与MSA的关联研究--取决于人类参考基因组的短读序列分析的陷阱。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-09-20 DOI: 10.1038/s10038-024-01293-y

Kenta Orimo, Jun Mitsui, Takashi Matsukawa, Masaki Tanaka, Junko Nomoto, Hiroyuki Ishiura, Yosuke Omae, Yosuke Kawai, Katsushi Tokunaga, Tatsushi Toda, Shoji Tsuji

引用次数: 0

Biallelic TXNDC15 variants associated with Joubert syndrome-related molar tooth sign and forebrain malformation. 与朱伯特综合征相关的臼齿征和前脑畸形有关的双叶TXNDC15变体。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-09-20 DOI: 10.1038/s10038-024-01290-1

Yukiko Kuroda, Tamaki Ikegawa, Ayumi Kato, Noriko Aida, Takuya Naruto, Kenji Kurosawa

{"title":"Biallelic TXNDC15 variants associated with Joubert syndrome-related molar tooth sign and forebrain malformation.","authors":"Yukiko Kuroda, Tamaki Ikegawa, Ayumi Kato, Noriko Aida, Takuya Naruto, Kenji Kurosawa","doi":"10.1038/s10038-024-01290-1","DOIUrl":"https://doi.org/10.1038/s10038-024-01290-1","url":null,"abstract":"TXNDC15 encodes thioredoxin domain-containing protein 15, a protein disulfide isomerase that plays a role in ciliogenesis. Biallelic TXNDC15 variants have been reported in six individuals of Meckel syndrome (MKS) with perinatal lethal phenotypes, but have not been reported in patients with Joubert syndrome (JS). Here, we describe a 1-year-old female patient with compound heterozygous TXNDC15 variants demonstrating cerebellar vermis hypoplasia with the molar tooth sign, mild holoprosencephaly, and cortical abnormalities. She had severe developmental delay and epilepsy. Her clinical features were similar to those of JS, but distinctive forebrain abnormalities were also noted including mild holoprosencephaly and cortical abnormalities, which have been reported in a severe form of ciliopathy. Biallelic TXNDC15 variants manifest as overlapping phenotypes of JS and MKS, including the molar tooth sign, cortical dysgenesis, and mild holoprosencephaly. This report supports the hypothesis that JS and MKS are spectrum ciliopathy disorders with overlapping causative genes and hypomorphic TXNDC15 variants might contribute to JS.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nationwide survey of the secondary findings in cancer genomic profiling: survey including liquid biopsy 全国癌症基因组剖析二次发现调查：包括液体活检在内的调查

IF 3.5 3区生物学

Journal of Human Genetics Pub Date : 2024-09-17 DOI: 10.1038/s10038-024-01294-x

Saki Shimada, Takahiro Yamada, Akari Minamoto, Manami Matsukawa, Ichiro Yabe, Hiroshi Tada, Katsutoshi Oda, Arisa Ueki, Satomi Higashigawa, Maki Morikawa, Yuki Sato, Akira Hirasawa, Masanobu Ogawa, Tomohiro Kondo, Masahiro Yoshioka, Masashi Kanai, Manabu Muto, Shinji Kosugi

{"title":"Nationwide survey of the secondary findings in cancer genomic profiling: survey including liquid biopsy","authors":"Saki Shimada, Takahiro Yamada, Akari Minamoto, Manami Matsukawa, Ichiro Yabe, Hiroshi Tada, Katsutoshi Oda, Arisa Ueki, Satomi Higashigawa, Maki Morikawa, Yuki Sato, Akira Hirasawa, Masanobu Ogawa, Tomohiro Kondo, Masahiro Yoshioka, Masashi Kanai, Manabu Muto, Shinji Kosugi","doi":"10.1038/s10038-024-01294-x","DOIUrl":"https://doi.org/10.1038/s10038-024-01294-x","url":null,"abstract":"We surveyed the status of the secondary finding (SF) disclosure in comprehensive genome profiling (CGP) in 2020. The situation has changed: increase in the number of hospitals that provide CGP, an update to the Comprehensive Tumor Genomic Profiling: Materials for Review of Secondary Findings (CTGPMRSF), and the addition of a liquid biopsy test, FoundationOne® Liquid CDx (F1L). Moreover, the actual situation was unclear because the 2020 survey did not include all designated and cooperative hospitals. Herein, we conducted a questionnaire survey of all designated-core, designated, and cooperative hospitals to identify the current status and challenges concerning SF in the CGP in 2022. A total of 82.1% of the hospitals responded and 77.7% of the response was from cooperative hospitals. Approximately 80% of the hospitals used CTGPMRSF. SF disclosure, confirmatory test implementation, and SF confirmation rates were 12.4%, 31.6%, and 46.6% for FoundationOne® CDx (F1CDx), respectively, and 6.8%, 31.8%, and 70.7% for F1L, respectively. The implementation rate of the confirmatory test was substantially higher in hospitals with genetic experts and in hospitals that could conduct confirmatory tests on the same day. Our survey provides insight into how SF is handled in Japan. The percentage of cases leading to confirmatory tests has gradually increased, although challenges such as insurance coverage limitations and varied understanding of SF among patients and healthcare providers persist. With the increasing use of whole-genome analysis, our findings will provide valuable insights into establishing an effective SF disclosure system.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":"18 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142262710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phenotypic spectrum of iron-sulfur cluster assembly gene IBA57 mutations: c.286 T > C identified as a hotspot mutation in Chinese patients with a stable natural history. 铁硫簇组装基因 IBA57 突变的表型谱：在自然病史稳定的中国患者中发现的 c.286 T > C 热点突变。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-09-03 DOI: 10.1038/s10038-024-01291-0

Huafang Jiang, Chaolong Xu, Ruoyu Duan, Zhimei Liu, Xiaotun Ren, Jiuwei Li, Chunhong Chen, Hongmei Wang, Tongli Han, Xiaojuan Tian, Xin Duan, Minhan Song, Tongyue Li, Fang Fang

{"title":"Phenotypic spectrum of iron-sulfur cluster assembly gene IBA57 mutations: c.286 T > C identified as a hotspot mutation in Chinese patients with a stable natural history.","authors":"Huafang Jiang, Chaolong Xu, Ruoyu Duan, Zhimei Liu, Xiaotun Ren, Jiuwei Li, Chunhong Chen, Hongmei Wang, Tongli Han, Xiaojuan Tian, Xin Duan, Minhan Song, Tongyue Li, Fang Fang","doi":"10.1038/s10038-024-01291-0","DOIUrl":"https://doi.org/10.1038/s10038-024-01291-0","url":null,"abstract":"Mutations in IBA57 disrupt iron-sulfur clusters maturation, causing a rare mitochondrial disease. Clinical manifestations vary from neonatal lethality to childhood-onset spastic paraparesis, yet the ethnic heterogeneity and natural history remain unclear, necessitating further exploration. This study aimed to delineate the genotype-phenotype correlation of IBA57 mutations by analyzing diverse clinical presentations. We report 11 Chinese patients and include literature-reported cases, totaling 61 patients enrolled for analysis. Clinical, neuroimaging, genetic, and disease progression information were collected. Among these, 46 presented as multiple mitochondrial dysfunctions syndrome 3 (MMDS3), with 58.7% originating from Chinese population. Based on disease course, we propose three clinical subtypes: neonatal, infant and childhood subtypes. Neonatal cases universally displayed hypotonia and respiratory distress at presentation, deceased within three months. Most infancy and childhood cases exhibited developmental regression and impaired motor function. Cavitating leukoencephalopathy was a typical neuroimaging finding in MMDS3 patients. The c.286 T > C mutation was reported in 85.2% of Chinese patients. A significantly lower mortality rate was observed compared to the non-Chinese group (P = 0.002), with a survival rate exceeding 90% at 5 years, indicating a relatively stable disease progression. Fifteen cases from three families manifested the spastic paraplegia 74 phenotype, demonstrating normal development before onset, with common clinical manifestations including spastic paraplegia (14/15), visual impairment (10/13), and peripheral neuropathy (9/13). In conclusion, this study indicates a hotspot mutation in Chinese and analyses the disease progression with different clinical subtypes.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigating common mutations in ATP7B gene and the prevalence of Wilson's disease in the Thai population using population-based genome-wide datasets. 利用基于人群的全基因组数据集调查泰国人群中 ATP7B 基因的常见突变和威尔逊氏病的患病率。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-08-28 DOI: 10.1038/s10038-024-01292-z

Paravee Own-Eium, Donniphat Dejsuphong, Prin Vathesatogkit, Piyamitr Sritara, Thanyachai Sura, Wichai Aekplakorn, Bhoom Suktitipat, Jakris Eu-Ahsunthornwattana

{"title":"Investigating common mutations in ATP7B gene and the prevalence of Wilson's disease in the Thai population using population-based genome-wide datasets.","authors":"Paravee Own-Eium, Donniphat Dejsuphong, Prin Vathesatogkit, Piyamitr Sritara, Thanyachai Sura, Wichai Aekplakorn, Bhoom Suktitipat, Jakris Eu-Ahsunthornwattana","doi":"10.1038/s10038-024-01292-z","DOIUrl":"https://doi.org/10.1038/s10038-024-01292-z","url":null,"abstract":"Wilson's disease (WD) is a rare metabolic disorder caused by variations in the ATP7B gene. It usually manifests hepatic, neurologic, and psychiatric symptoms due to excessive copper accumulation. The prevalence of WD and its common variants differ across populations. This study aimed to examine these aspects of WD within the Thai population, where information has been limited. We reviewed ClinVar and the Wilson Disease Mutation Database, organizing variants classified as pathogenic or likely pathogenic in one or both databases as \"relaxed\" and \"strict\" lists. Allele frequencies were estimated from genotyping array data (Asian Screening Array: ASA; Illumina Corp, CA) of 6291 Thai subjects, which also underwent genotype imputation. The prevalence of WD in the Thai population was estimated assuming Hardy-Weinberg Equilibrium. The strict list yielded a prevalence of 1/24,128 (carrier frequency=1/78), while the relaxed list yielded a prevalence of 1/9971 (carrier frequency=1/50). The most common WD variants in Thai subjects were c.2333 G > T, c.3443 T > C, and c.813 C > A from the strict list, and c.3316 G > A and c.2605 G > A from the relaxed list. The ASA chip covered approximately 59 and 24% of WD variants from the strict and relaxed lists, respectively. Based on the estimated prevalence, a carrier screening program for WD is not currently required in Thailand. However, as genotyping services become more affordable and accessible, such a program would facilitate early identification, treatment, and prevention of WD.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Artificial intelligence in medical genomics 医学基因组学中的人工智能。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-08-27 DOI: 10.1038/s10038-024-01282-1

Yoichiro Kamatani, Tadashi Kaname

引用次数: 0

Healthy lifestyle practice correlates with decreased obesity prevalence in individuals with high polygenic risk: TMM CommCohort study. 健康生活方式与多基因高风险人群肥胖患病率下降相关：TMM社区队列研究。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-08-22 DOI: 10.1038/s10038-024-01280-3

Yoichi Sutoh, Tsuyoshi Hachiya, Yayoi Otsuka-Yamasaki, Shohei Komaki, Shiori Minabe, Hideki Ohmomo, Makoto Sasaki, Atsushi Shimizu

{"title":"Healthy lifestyle practice correlates with decreased obesity prevalence in individuals with high polygenic risk: TMM CommCohort study.","authors":"Yoichi Sutoh, Tsuyoshi Hachiya, Yayoi Otsuka-Yamasaki, Shohei Komaki, Shiori Minabe, Hideki Ohmomo, Makoto Sasaki, Atsushi Shimizu","doi":"10.1038/s10038-024-01280-3","DOIUrl":"https://doi.org/10.1038/s10038-024-01280-3","url":null,"abstract":"Obesity and overweight, fundamental components of the metabolic syndrome, predispose individuals to lifestyle-related diseases. The extent to which adopting healthy lifestyles can reduce obesity risk, even in those with a high genetic risk, remains uncertain. Our aim was to assess the extent to which lifestyle modifications can improve outcomes in individuals with a high polygenic score (PGS) for obesity. We quantified the genetic risk of obesity using PGSs. Four datasets from the Tohoku Medical Megabank Community-Based Cohort (TMM CommCohort) were employed in the study. One dataset (n = 9958) was used to select the best model for calculating PGS. The remaining datasets (total n = 69,341) were used in a meta-analysis to validate the model and to evaluate associated risks. The odds ratio (OR) for obesity risk in the intermediate (11th-90th percentiles in the dataset) and high PGS categories (91st-100th) was 2.27 [95% confidence intervals: 2.12-2.44] and 4.83 [4.45-5.25], respectively, compared to that in the low PGS category (1st-10th). Trend analysis showed that an increase in leisure-time physical activity was significantly associated with reduced obesity risk across all genetic risk categories, representing an OR of 0.9 [0.87-0.94] even among individuals in the high PGS category. Similarly, sodium intake displayed a positive association with obesity across all genetic risk categories, yielding an OR of 1.24 [1.17-1.31] in the high PGS category. The risk of obesity was linked to the adoption of healthy lifestyles, even in individuals with high PGS. Our results may provide perspectives for integrating PGSs into preventive medicine.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hydrops fetalis due to loss of function of hNav1.4 channel via compound heterozygous variants. 通过复合杂合变体导致 hNav1.4 通道功能缺失引起的胎儿水肿。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-08-21 DOI: 10.1038/s10038-024-01284-z

Tomoya Kubota, Miho Nagata, Kazuko Takagi, Yasuki Ishihara, Kurumi Kojima, Yuka Uchikura, Reina Yamamoto, Ayumi Yonei, Erina Ozaki, Natsuki Kira, Satoe Takahashi, Kazuaki Homma, Yohei Miyashita, Minenori Eguchi-Ishimae, Norio Sakai, Yohihiro Asano, Yasushi Sakata, Keiichi Ozono, Mariko Eguchi, Masanori P Takahashi

{"title":"Hydrops fetalis due to loss of function of hNav1.4 channel via compound heterozygous variants.","authors":"Tomoya Kubota, Miho Nagata, Kazuko Takagi, Yasuki Ishihara, Kurumi Kojima, Yuka Uchikura, Reina Yamamoto, Ayumi Yonei, Erina Ozaki, Natsuki Kira, Satoe Takahashi, Kazuaki Homma, Yohei Miyashita, Minenori Eguchi-Ishimae, Norio Sakai, Yohihiro Asano, Yasushi Sakata, Keiichi Ozono, Mariko Eguchi, Masanori P Takahashi","doi":"10.1038/s10038-024-01284-z","DOIUrl":"https://doi.org/10.1038/s10038-024-01284-z","url":null,"abstract":"Hydrops fetalis, characterized by abnormal fluid accumulation in fetuses, presents a significant risk of stillbirth and neonatal mortality. Although the etiology of nonimmune hydrops fetalis (NIHF) is multifaceted, recent studies have highlighted genetic factors as crucial determinants. This study focused on a family with three consecutive stillbirths, each with pronounced hydrops fetalis. Using whole-exome sequencing (WES), we identified compound heterozygous variants of the SCN4A gene encoding the voltage-gated sodium channel of the skeletal muscle (hNav1.4), c.2429T>A p.L810Q and c.4556T>C p.F1519S, in all three deceased infants. A functional analysis conducted using the whole-cell patch-clamp technique revealed loss-of-function defects in both variant channels, with F1519S exhibiting a complete loss of ionic current and L810Q showing a reduced channel opening. These findings support the pathogenicity of SCN4A variants in NIHF and underscore the significance of functional studies in elucidating genotype-phenotype correlations. Furthermore, our study emphasizes the diagnostic value of WES in cases of NIHF in where standard genetic testing fails to identify causative variants.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Contribution of rare variants to heritability of a disease is much greater than conventionally estimated: modification of allele distribution model. 罕见变异对疾病遗传性的贡献远大于传统估计：等位基因分布模型的修正。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-08-20 DOI: 10.1038/s10038-024-01281-2

Yoshiro Nagao

{"title":"Contribution of rare variants to heritability of a disease is much greater than conventionally estimated: modification of allele distribution model.","authors":"Yoshiro Nagao","doi":"10.1038/s10038-024-01281-2","DOIUrl":"https://doi.org/10.1038/s10038-024-01281-2","url":null,"abstract":"\"Missing heritability\" is a current problem in human genetics. I previously reported a method to estimate heritability of a polymorphism (hp2) for a common disease without calculating the genetic variance under dominant and the recessive models. Here, I extend the method to the co-dominant model and carry out trial calculations of hp2. I also calculate hp2 applying the allele distribution model originally reported by Pawitan et al. for comparison as a conventional method. But unexpectedly, hp2 calculated for rare variants with high odds ratios was much higher than the calculated values with the allele distribution model. Also, while examining the basis for the difference in calculated hp2, I noticed that conventional methods use the allele frequency (AF) of a variant in the general population to calculate the genetic variance of that variant. However, this implicitly assumes that the unaffected are included among the phenotypes of the disease - an assumption that is inconsistent with case-control studies in which unaffected individuals belong to the control (unaffected) group. Therefore, I modified the allele distribution model by using the AF in the patient population. Consequently, the hp2 of rare variants calculated with the modified allele distribution model was quite high. Recalculating hp2 of several rare variants reported in the literature with the modified allele distribution model yielded results were 3.2 - 53.7 times higher than the hp2 calculated with the original allele distribution model. These results suggest that the contribution of rare variants to heritability of a disease has been considerably underestimated.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0