A comprehensive survey of genetic variation in 20,691 subjects from four large cohorts.
paper
Cited
Public
- Authors
- LindstrΓΆm, Sara; Loomis, Stephanie; Turman, Constance; Huang, Hongyan; Huang, Jinyan; Aschard, Hugues; Chan, Andrew T; Choi, Hyon; Cornelis, Marilyn; Curhan, Gary; De Vivo, Immaculata; Eliassen, A Heather; Fuchs, Charles; Gaziano, Michael; Hankinson, Susan E; Hu, Frank; Jensen, Majken; Kang, Jae H; Kabrhel, Christopher; Liang, Liming; Pasquale, Louis R; Rimm, Eric; Stampfer, Meir J; Tamimi, Rulla M; Tworoger, Shelley S; Wiggs, Janey L; Hunter, David J; Kraft, Peter
- Year
- 2017
- Journal
- PloS one
- PMID
- 28301549
- DOI
- 10.1371/journal.pone.0173997
- PMCID
- PMC5354293
The Nurses' Health Study (NHS), Nurses' Health Study II (NHSII), Health Professionals Follow Up Study (HPFS) and the Physicians Health Study (PHS) have collected detailed longitudinal data on multiple exposures and traits for approximately 310,000 study participants over the last 35 years. Over 160,000 study participants across the cohorts have donated a DNA sample and to date, 20,691 subjects have been genotyped as part of genome-wide association studies (GWAS) of twelve primary outcomes. However, these studies utilized six different GWAS arrays making it difficult to conduct analyses of secondary phenotypes or share controls across studies. To allow for secondary analyses of these data, we have created three new datasets merged by platform family and performed imputation using a common reference panel, the 1,000 Genomes Phase I release. Here, we describe the methodology behind the data merging and imputation and present imputation quality statistics and association results from two GWAS of secondary phenotypes (body mass index (BMI) and venous thromboembolism (VTE)). We observed the strongest BMI association for the FTO SNP rs55872725 (Ξ² = 0.45, p = 3.48x10-22), and using a significance level of p = 0.05, we replicated 19 out of 32 known BMI SNPs. For VTE, we observed the strongest association for the rs2040445 SNP (OR = 2.17, 95% CI: 1.79-2.63, p = 2.70x10-15), located downstream of F5 and also observed significant associations for the known ABO and F11 regions. This pooled resource can be used to maximize power in GWAS of phenotypes collected across the cohorts and for studying gene-environment interactions as well as rare phenotypes and genotypes.
Overlap in SNPs across genotype platforms.
Fig 2
Imputation quality score by minor allele frequency for the three platform families.
QQ-plot for GWAS analysis of body mass index based on 20,283 individuals.
Manhattan plot for GWAS analysis of body mass index based on 20,283 individuals.
Associations for known body mass index SNPs based on 20,283 individuals.
QQ-plot for GWAS analysis of venous thromboembolism based on 1,364 cases and 17,628 controls.
Manhattan plot for GWAS analysis of venous thromboembolism based on 1,364 cases and 17,628 controls.
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| Obesity, Adiposity, and Risk of Symptomatic Gallstone Disease According to Genetic Susceptibility. | Lim J et al. | β | 2022 | β |
| Oral postmenopausal hormone therapy and genetic risk on venous thromboembolism: gene-hormone interaction results from a large prospective cohort study. | Kim J et al. | β | 2022 | β |
| Polygenic scores, diet quality, and type 2 diabetes risk: An observational study among 35,759 adults from 3 US cohorts. | Merino J et al. | β | 2022 | β |
| Reduced cardiovascular risks in women with endometriosis or polycystic ovary syndrome carrying a common functional IGF1R variant. | Powell MJ et al. | β | 2022 | β |
| Sex differences, cross-ancestry generalizability, and noise-smoking interactions in the polygenic architecture of hearing loss in adults | De Angelis F et al. | β | 2022 | β |
| Vigorous Physical Activity and Cognitive Trajectory Later in Life: Prospective Association and Interaction by Apolipoprotein E e4 in the Nurses' Health Study. | Fassier P et al. | β | 2022 | β |
| A Genome-Wide Association Study of Childhood Body Fatness. | Warner ET et al. | β | 2021 | β |
| Bitter taste receptors: Genes, evolution and health. | Wooding SP et al. | β | 2021 | β |
| Genetic determinants of liking and intake of coffee and other bitter foods and beverages. | Cornelis MC et al. | β | 2021 | β |
| Identifying Susceptibility Loci for Cutaneous Squamous Cell Carcinoma Using a Fast Sequence Kernel Association Test. | Huang M et al. | β | 2021 | β |
| Instrumental variable estimation for a time-varying treatment and a time-to-event outcome via structural nested cumulative failure time models. | Shi J et al. | β | 2021 | β |
| Risk prediction models for colorectal cancer: Evaluating the discrimination due to added biomarkers. | Fang Z et al. | β | 2021 | β |
| Additive and Multiplicative Interactions Between Genetic Risk Score and Family History and Lifestyle in Relation to Risk of Type 2 Diabetes. | Ding M et al. | β | 2020 | β |
| Colorectal cancer susceptibility variants and risk of conventional adenomas and serrated polyps: results from three cohort studies. | Hang D et al. | β | 2020 | β |
| Genetic factors and risk of type 2 diabetes among women with a history of gestational diabetes: findings from two independent populations. | Li M et al. | β | 2020 | β |
| Genome-Wide Association Study for Urinary and Fecal Incontinence in Women. | Penney KL et al. | β | 2020 | β |
| The Mediterranean diet, plasma metabolome, and cardiovascular disease risk. | Li J et al. | β | 2020 | β |
| Efficient cross-trait penalized regression increases prediction accuracy in large cohorts using secondary phenotypes. | Chung W et al. | β | 2019 | β |
| Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism. | LindstrΓΆm S et al. | β | 2019 | β |
| Interaction between apolipoprotein E genotype and hypertension on cognitive function in older women in the Nurses' Health Study. | Kim IY et al. | β | 2019 | β |
| Joint Analysis of Multiple Interaction Parameters in Genetic Association Studies. | Kim J et al. | β | 2019 | β |
| A genome-wide association study of energy intake and expenditure. | Jiang L et al. | β | 2018 | β |
| Genetic variants of gestational diabetes mellitus: a study of 112 SNPs among 8722 women in two independent populations. | Ding M et al. | β | 2018 | β |
| Interaction of a genetic risk score with physical activity, physical inactivity, and body mass index in relation to venous thromboembolism risk. | Kim J et al. | β | 2018 | β |
| Joint effects of fatty acid desaturase 1 polymorphisms and dietary polyunsaturated fatty acid intake on circulating fatty acid proportions. | Juan J et al. | β | 2018 | β |
| Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria. | Day F et al. | β | 2018 | β |
| Polygenic risk score of shorter telomere length and risk of depression and anxiety in women. | Chang SC et al. | β | 2018 | β |
| Genome-Wide Association Studies of Multiple Keratinocyte Cancers. | Pardo LM et al. | β | 2017 | β |
| A genome-wide investigation of food addiction. | Cornelis MC et al. | β | 2016 | β |
| Sniffing out significant "Pee values": genome wide association study of asparagus anosmia. | Markt SC et al. | β | 2016 | β |