A comprehensive map of genetic variation in the world’s largest ethnic group - Han Chinese

AbstractAs are most non-European populations around the globe, the Han Chinese are relatively understudied in population and medical genetics studies. From low-coverage whole-genome sequencing of 11,670 Han Chinese women we present a catalog of 25,057,223 variants, including 548,401 novel variants that are seen at least 10 times in our dataset. Individuals from our study come from 19 out of 22 provinces across China, allowing us to study population structure, genetic ancestry, and local adaptation in Han Chinese. We identify previously unrecognized population structure along the East-West axis of China and report unique signals of admixture across geographical space, such as European influences among the Northwestern provinces of China. Finally, we identified a number of highly differentiated loci, indicative of local adaptation in the Han Chinese. In particular, we detected extreme differentiation among the Han Chinese at MTHFR, ADH7, and FADS loci, suggesting that these loci may not be specifically selected in Tibetan and Inuit populations as previously suggested. On the other hand, we find that Neandertal ancestry does not vary significantly across the provinces, consistent with admixture prior to the dispersal of modern Han Chinese. Furthermore, contrary to a previous report, Neandertal ancestry does not explain a significant amount of heritability in depression. Our findings provide the largest genetic data set so far made available for Han Chinese and provide insights into the history and population structure of the world’s largest ethnic group.

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A Comprehensive Map of Genetic Variation in the World’s Largest Ethnic Group—Han Chinese

Molecular Biology and Evolution ◽

10.1093/molbev/msy170 ◽

2018 ◽

Vol 35 (11) ◽

pp. 2736-2750 ◽

Cited By ~ 25

Author(s):

Charleston W K Chiang ◽

Serghei Mangul ◽

Christopher Robles ◽

Sriram Sankararaman

Keyword(s):

Population Structure ◽

Ethnic Group ◽

Chinese Women ◽

Isolation By Distance ◽

General Pattern ◽

Han Chinese ◽

Data Set ◽

Novel Variants ◽

Study Population ◽

Low Coverage

Abstract As are most non-European populations, the Han Chinese are relatively understudied in population and medical genetics studies. From low-coverage whole-genome sequencing of 11,670 Han Chinese women we present a catalog of 25,057,223 variants, including 548,401 novel variants that are seen at least 10 times in our data set. Individuals from this data set came from 24 out of 33 administrative divisions across China (including 19 provinces, 4 municipalities, and 1 autonomous region), thus allowing us to study population structure, genetic ancestry, and local adaptation in Han Chinese. We identified previously unrecognized population structure along the East–West axis of China, demonstrated a general pattern of isolation-by-distance among Han Chinese, and reported unique regional signals of admixture, such as European influences among the Northwestern provinces of China. Furthermore, we identified a number of highly differentiated, putatively adaptive, loci (e.g., MTHFR, ADH7, and FADS, among others) that may be driven by immune response, climate, and diet in the Han Chinese. Finally, we have made available allele frequency estimates stratified by administrative divisions across China in the Geography of Genetic Variant browser for the broader community. By leveraging the largest currently available genetic data set for Han Chinese, we have gained insights into the history and population structure of the world’s largest ethnic group.

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Dietary Choline Intake during Pregnancy and PEMT rs7946 Polymorphism on Risk of Preterm Birth: A Case-Control Study

Annals of Nutrition and Metabolism ◽

10.1159/000507472 ◽

2021 ◽

pp. 1-10

Author(s):

Jie Zhu ◽

Yu-Hong Liu ◽

Xiang-Long He ◽

Martin Kohlmeier ◽

Li-Li Zhou ◽

...

Keyword(s):

Preterm Birth ◽

Case Control Study ◽

Chinese Women ◽

Case Control ◽

Han Chinese ◽

Food Frequency ◽

Term Delivery ◽

Choline Intake ◽

Dietary Choline ◽

Control Study

Introduction and Aims: Choline-metabolizing genetic variation may interact with choline intake on fetal programming and pregnancy outcome. This case-control study aims to explore the association of maternal choline consumption and phosphatidylethanolamine N-methyltransferase (PEMT) gene polymorphism rs7946 with preterm birth risk. Methods: 145 Han Chinese women with preterm delivery and 157 Han Chinese women with term delivery were recruited in Shanghai. Dietary choline intake during pregnancy was assessed using a validated food frequency questionnaire. Additionally, DNA samples were genotyped for PEMT rs7946 (G5465A) with plasma homocysteine (Hcy) levels measured. Results: Compared with the lowest quartile of choline intake, women within the highest consumption quartile had adjusted odds ratio (aOR) for preterm birth of 0.48 (95% confidence interval, CI [0.24, 0.95]). There was a significant interaction between maternal choline intake and PEMT rs7946 (p for interaction = 0.04), where the AA genotype carriers who consumed the energy-adjusted choline <255.01 mg/day had aOR for preterm birth of 3.75 (95% CI [1.24, 11.35]), compared to those with GG genotype and choline intake >255.01 mg/day during pregnancy. Additionally, the greatest elevated plasma Hcy was found in the cases with AA genotype and choline consumption <255.01 mg/day (p < 0.001). Conclusion: The AA genotype of PEMT rs7946 may be associated with increased preterm birth in these Han Chinese women with low choline intake during pregnancy.

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Common variants in MAEA gene contributed the susceptibility to osteoporosis in Han Chinese postmenopausal women

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-020-02140-4 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Xuan Cai ◽

Jun Dong ◽

Teng Lu ◽

Liqiang Zhi ◽

Xijing He

Keyword(s):

Postmenopausal Women ◽

Chinese Women ◽

Han Chinese ◽

Blood Levels ◽

Nucleotide Polymorphisms ◽

Mineral Density ◽

Association Analyses ◽

Metabolism Disorder ◽

Increased Risk ◽

Chinese Postmenopausal Women

Abstract Background Osteoporosis (OP) is a complex bone metabolism disorder characterized by the loss of bone minerals and an increased risk of bone fracture. A recent study reported the relationship of the macrophage erythroblast attacher gene (MAEA) with low bone mineral density in postmenopausal Japanese women. Our study aimed to investigate the association of MAEA with postmenopausal osteoporosis (PMOP) in Han Chinese individuals. Methods A total of 968 unrelated postmenopausal Chinese women comprising 484 patients with PMOP and 484 controls were recruited. Four tag single nucleotide polymorphisms (SNPs) that covered the gene region of MAEA were chosen for genotyping. Single SNP and haplotypic association analyses were performed, and analysis of variance was conducted to test the correlation between blood MAEA protein level and genotypes of associated SNPs. Results SNP rs6815464 was significantly associated with the risk of PMOP. The C allele of rs6815464 was strongly correlated with the decreased risk of PMOP in our study subjects (OR[95% CI]=0.75[0.63-0.89], P=0.0015). Significant differences in MAEA protein blood levels among genotypes of SNP rs6815464 were identified in both the PMOP (F=6.82, P=0.0012) and control groups (F=11.5, P=0.00001). The C allele was positively associated with decreased MAEA protein levels in blood. Conclusion This case-control study on Chinese postmenopausal women suggested an association between SNP rs6815464 of MAEA and PMOP. Further analyses showed that genotypes of SNP rs6815464 were also associated with the blood level of MAEA protein.

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Analysis of cyclin-dependent kinase inhibitor 1B mutation in Han Chinese women with premature ovarian failure

Reproductive BioMedicine Online ◽

10.1016/j.rbmo.2010.04.025 ◽

2010 ◽

Vol 21 (2) ◽

pp. 212-214 ◽

Cited By ~ 6

Author(s):

Binbin Wang ◽

Feng Ni ◽

Lin Li ◽

Zhaolian Wei ◽

Xianglong Zhu ◽

...

Keyword(s):

Premature Ovarian Failure ◽

Kinase Inhibitor ◽

Chinese Women ◽

Ovarian Failure ◽

Han Chinese ◽

Cyclin Dependent Kinase ◽

Cyclin Dependent Kinase Inhibitor

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Erratum: Corrigendum: Genome-wide association study identifies new susceptibility loci for epithelial ovarian cancer in Han Chinese women

Nature Communications ◽

10.1038/ncomms6828 ◽

2014 ◽

Vol 5 (1) ◽

Cited By ~ 3

Author(s):

Kexin Chen ◽

Hongxia Ma ◽

Lian Li ◽

Rongyu Zang ◽

Cheng Wang ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Association Study ◽

Genome Wide Association Study ◽

Chinese Women ◽

Han Chinese ◽

Genome Wide Association ◽

Susceptibility Loci ◽

Genome Wide

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Empirical Evaluation of Genetic Clustering Methods Using Multilocus Genotypes From 20 Chicken Breeds

Genetics ◽

10.1093/genetics/159.2.699 ◽

2001 ◽

Vol 159 (2) ◽

pp. 699-713

Author(s):

Noah A Rosenberg ◽

Terry Burke ◽

Kari Elo ◽

Marcus W Feldman ◽

Paul J Freidlin ◽

...

Keyword(s):

Cluster Analysis ◽

Population Structure ◽

Clustering Algorithm ◽

Empirical Evaluation ◽

Unknown Origin ◽

Clustering Methods ◽

Genetic Cluster ◽

Data Set ◽

Multilocus Genotypes ◽

Chicken Breeds

Abstract We tested the utility of genetic cluster analysis in ascertaining population structure of a large data set for which population structure was previously known. Each of 600 individuals representing 20 distinct chicken breeds was genotyped for 27 microsatellite loci, and individual multilocus genotypes were used to infer genetic clusters. Individuals from each breed were inferred to belong mostly to the same cluster. The clustering success rate, measuring the fraction of individuals that were properly inferred to belong to their correct breeds, was consistently ~98%. When markers of highest expected heterozygosity were used, genotypes that included at least 8–10 highly variable markers from among the 27 markers genotyped also achieved >95% clustering success. When 12–15 highly variable markers and only 15–20 of the 30 individuals per breed were used, clustering success was at least 90%. We suggest that in species for which population structure is of interest, databases of multilocus genotypes at highly variable markers should be compiled. These genotypes could then be used as training samples for genetic cluster analysis and to facilitate assignments of individuals of unknown origin to populations. The clustering algorithm has potential applications in defining the within-species genetic units that are useful in problems of conservation.

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Association of the CACNA2D2 gene with schizophrenia in Chinese Han population

PeerJ ◽

10.7717/peerj.8521 ◽

2020 ◽

Vol 8 ◽

pp. e8521

Author(s):

Yingli Fu ◽

Na Zhou ◽

Wei Bai ◽

Yaoyao Sun ◽

Xin Chen ◽

...

Keyword(s):

Calcium Channel ◽

Chinese Women ◽

Han Chinese ◽

Type I ◽

Genotype Distribution ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Increased Risk ◽

Significant Difference

Background Schizophrenia (SCZ) is a severely complex psychiatric disorder in which ~80% can be explained by genetic factors. Single nucleotide polymorphisms (SNPs) in calcium channel genes are potential genetic risk factors for a spectrum of psychiatric disorders including SCZ. This study evaluated the association between SNPs in the voltage-gated calcium channel auxiliary subunit alpha2delta 2 gene (CACNA2D2) and SCZ in the Han Chinese population of Northeast China. Methods A total of 761 SCZ patients and 775 healthy controls were involved in this case-control study. Three SNPs (rs3806706, rs45536634 and rs12496815) of CACNA2D2 were genotyped by the MALDI-TOF-MS technology. Genotype distribution and allele frequency differences between cases and controls were tested by Chi-square (χ2) in males and females respectively using SPSS 24.0 software. Linkage disequilibrium and haplotype analyses were conducted using Haploview4.2. The false discovery rate correction was utilized to control for Type I error by R3.2.3. Results There was a significant difference in allele frequencies (χ2 = 9.545, Padj = 0.006) and genotype distributions (χ2 = 9.275, Padj = 0.006) of rs45536634 between female SCZ patients and female healthy controls after adjusting for multiple comparisons. Minor allele A (OR = 1.871, 95% CI [1.251–2.798]) and genotype GA + AA (OR = 1.931, 95% CI [1.259–2.963]) were associated with an increased risk of SCZ. Subjects with haplotype AG consisting of rs45536634 and rs12496815 alleles had a higher risk of SCZ (OR = 1.91, 95% CI [1.26–2.90]) compared those with other haplotypes. Conclusions This study provides evidence that CACNA2D2 polymorphisms may influence the susceptibility to SCZ in Han Chinese women.

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