PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses

Purcell, Shaun; Neale, Benjamin M.; Todd-Brown, Katherine; Thomas, Lisa; Ferreira, Manuel; Bender, D. B.; Maller, Julian; Sklar, Pamela; Bakker, Paul I. W. de; Daly, Mark J.; Sham, Pak C.

doi:10.1086/519795

Cited by 28,406 publications

(28,231 citation statements)

References 36 publications

Supporting

Mentioning

27,133

Contrasting

Unclassified

101

Order By: Relevance

“…To define a lead SNP of each locus, the association results of a GWAS stage with P ‐values <1 × 10 −5 were grouped based on the LD structure of the HapMap release 28 CEU dataset using PLINK (settings r 2 >0.01, 1 Mb distance) (Purcell et al ., 2007). Due to the strong association of the IGFBP3 locus with IGFBP‐3, only one lead SNP was selected regardless of several grouped results.…”

Section: Methodsmentioning

confidence: 99%

Genomewide meta‐analysis identifies loci associated with IGF ‐I and IGFBP ‐3 levels with impact on age‐related traits

Teumer¹,

Qi²,

Nethander³

et al. 2016

Aging Cell

View full text Add to dashboard Cite

SummaryThe growth hormone/insulin‐like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF‐related proteins including IGF‐I and IGF‐binding protein‐3 (IGFBP‐3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30 884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF‐I and IGFBP‐3 concentrations (IGF1, IGFBP3,GCKR,TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype–phenotype associations between men and women, were found only for associations of IGFBP‐3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF‐I and IGFBP‐3 concentrations. The IGF‐I‐decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90 years. The known longevity‐associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF‐I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF‐I‐ and IGFBP‐3‐associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF‐I and IGFBP‐3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity‐associated loci.

show abstract

Section: Methodsmentioning

confidence: 99%

Genomewide meta‐analysis identifies loci associated with IGF ‐I and IGFBP ‐3 levels with impact on age‐related traits

Teumer¹,

Qi²,

Nethander³

et al. 2016

Aging Cell

View full text Add to dashboard Cite

show abstract

“…Tests for Hardy–Weinberg equilibrium, linkage disequilibrium, genotype missingness and allelic, and genotypic frequency comparisons were conducted using PLINK [Purcell et al, 2007]. Three failed genotyping or Hardy–Weinberg equilibrium ( P < 0.001) in either the US or Australian at‐risk sample (rs12912251, rs4332037, rs7578035), and one was in linkage disequilibrium with another SNP (rs11168751 with rs2070615; r 2 = 0.141, D′ = 1.0).…”

Section: Methodsmentioning

confidence: 99%

Assessment of first and second degree relatives of individuals with bipolar disorder shows increased genetic risk scores in both affected relatives and young At‐Risk Individuals

Fullerton

Koller

Edenberg

et al. 2015

American J of Med Genetics Pt B

View full text Add to dashboard Cite

Recent studies have revealed the polygenic nature of bipolar disorder (BP), and identified common risk variants associated with illness. However, the role of common polygenic risk in multiplex families has not previously been examined. The present study examined 249 European‐ancestry families from the NIMH Genetics Initiative sample, comparing subjects with narrowly defined BP (excluding bipolar II and recurrent unipolar depression; n = 601) and their adult relatives without BP (n = 695). Unrelated adult controls (n = 266) were from the NIMH TGEN control dataset. We also examined a prospective cohort of young (12–30 years) offspring and siblings of individuals with BPI and BPII disorder (at risk; n = 367) and psychiatrically screened controls (n = 229), ascertained from five sites in the US and Australia and assessed with standardized clinical protocols. Thirty‐two disease‐associated SNPs from the PGC‐BP Working Group report (2011) were genotyped and additive polygenic risk scores (PRS) derived. We show increased PRS in adult cases compared to unrelated controls (P = 3.4 × 10−5, AUC = 0.60). In families with a high‐polygenic load (PRS score ≥32 in two or more subjects), PRS distinguished cases with BPI/SAB from other relatives (P = 0.014, RR = 1.32). Secondly, a higher PRS was observed in at‐risk youth, regardless of affected status, compared to unrelated controls (GEE‐χ2 = 5.15, P = 0.012). This report is the first to explore common polygenic risk in multiplex families, albeit using only a small number of robustly associated risk variants. We show that individuals with BP have a higher load of common disease‐associated variants than unrelated controls and first‐degree relatives, and illustrate the potential utility of PRS assessment in a family context. © 2015 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

show abstract

“…Quality control (QC) was performed in Plink (http://pngu.mgh.harvard.edu/~purcell/plink/; Purcell et al ., 2007) and samples were evaluated and excluded based on call rate (call rate < 98.5%), inconsistencies between genotypic and phenotypic sex, and family relationships (proportional IBD > 0.1875). Of the 673 originally included samples, 662 samples remained after the genotype‐based QC.…”

Section: Methodsmentioning

confidence: 99%

“…Data on CNV burden, that is, the number of CNVs, the average CNV length, and the total CNV length, were retrieved for each individual using Plink (http://pngu.mgh.harvard.edu/~purcell/plink/; Purcell et al ., 2007). …”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Copy number variation associates with mortality in long‐lived individuals: a genome‐wide assessment

et al. 2015

View full text Add to dashboard Cite

SummaryCopy number variants (CNVs) represent a significant source of genetic variation in the human genome and have been implicated in numerous diseases and complex traits. To date, only a few studies have investigated the role of CNVs in human lifespan. To investigate the impact of CNVs on prospective mortality at the extreme end of life, where the genetic component of lifespan appears most profound, we analyzed genomewide CNV data in 603 Danish nonagenarians and centenarians (mean age 96.9 years, range 90.0–102.5 years). Replication was performed in 500 long‐lived individuals from the Leiden Longevity Study (mean age 93.2 years, range 88.9–103.4 years). First, we assessed the association between the CNV burden of each individual (the number of CNVs, the average CNV length, and the total CNV length) and mortality and found a significant increase in mortality per 10 kb increase in the average CNV length, both for all CNVs (hazard ratio (HR) = 1.024, P = 0.002) and for duplications (HR = 1.011, P = 0.005), as well as per 100 kb increase in the total length of deletions (HR = 1.009, P = 0.0005). Next, we assessed the relation between specific deletions and duplications and mortality. Although no genome–wide significant associations were discovered, we identified six deletions and one duplication that showed consistent association with mortality in both or either of the sexes across both study populations. These results indicate that the genome–wide CNV burden, specifically the average CNV length and the total CNV length, associates with higher mortality in long‐lived individuals.

show abstract

PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses

Cited by 28,406 publications

References 36 publications

Genomewide meta‐analysis identifies loci associated with IGF ‐I and IGFBP ‐3 levels with impact on age‐related traits

Genomewide meta‐analysis identifies loci associated with IGF ‐I and IGFBP ‐3 levels with impact on age‐related traits

Assessment of first and second degree relatives of individuals with bipolar disorder shows increased genetic risk scores in both affected relatives and young At‐Risk Individuals

Copy number variation associates with mortality in long‐lived individuals: a genome‐wide assessment

Contact Info

Product

Resources

About