ProfessorMarkLathrop

Jun G, Ibrahim-Verbaas CA, Vronskaya M, Lambert JC, Chung J, Naj AC, Kunkle BW, Wang LS, Bis JC, Bellenguez C, Harold D, Lunetta KL, Destefano AL, Grenier-Boley B, Sims R, Beecham GW, Smith AV, Chouraki V, Hamilton-Nelson KL, Ikram MA, Fievet N, Denning N, Martin ER, Schmidt H, Kamatani Y, Dunstan ML, Valladares O, Laza AR, Zelenika D, Ramirez A, Foroud TM, Choi SH, Boland A, Becker T, Kukull WA, van der Lee SJ, Pasquier F, Cruchaga C, Beekly D, Fitzpatrick AL, Hanon O, Gill M, Barber R, Gudnason V, Campion D, Love S, Bennett DA, Amin N, Berr C, Tsolaki M, Buxbaum JD, Lopez OL, Deramecourt V, Fox NC, Cantwell LB, Tárraga L, Dufouil C, Hardy J, Crane PK, Eiriksdottir G, Hannequin D, Clarke R, Evans D, Mosley TH, Letenneur L, Brayne C, Maier W, De Jager P, Emilsson V, Dartigues JF, Hampel H, Kamboh MI, de Bruijn RF, Tzourio C, Pastor P, Larson EB, Rotter JI, O'Donovan MC, Montine TJ, Nalls MA, Mead S, Reiman EM, Jonsson PV, Holmes C, St George-Hyslop PH, Boada M, Passmore P, Wendland JR, Schmidt R, Morgan K, Winslow AR, Powell JF, Carasquillo M, Younkin SG, Jakobsdóttir J, Kauwe JS, Wilhelmsen KC, Rujescu D, Nöthen MM, Hofman A, Jones L, IGAP Consortium, Haines JL, Psaty BM, Van Broeckhoven C, Holmans P, Launer LJ, Mayeux R, Lathrop M, Goate AM, Escott-Price V, Seshadri S, Pericak-Vance MA, Amouyel P, Williams J, van Duijn CM, Schellenberg GD, Farrer LAet al., 2016, A novel Alzheimer disease locus located near the gene encoding tau protein., Molecular Psychiatry, Vol: 21, Pages: 108-117, ISSN: 1476-5578

APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ɛ4+ (10 352 cases and 9207 controls) and APOE ɛ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ɛ4 status. Suggestive associations (P<1 × 10(-4)) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ɛ4+: 1250 cases and 536 controls; APOE ɛ4-: 718 cases and 1699 controls). Among APOE ɛ4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10(-9)). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ɛ4+ subjects (CR1 and CLU) or APOE ɛ4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P ⩽ 1.3 × 10(-8)), frontal cortex (P ⩽ 1.3 × 10(-9)) and temporal cortex (P⩽1.2 × 10(-11)). Rs113986870 is also

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Meyer BM, Huemer J, Rabl U, Boubela RN, Kalcher K, Berger A, Banaschewski T, Barker G, Bokde A, Büchel C, Conrod P, Desrivières S, Flor H, Frouin V, Gallinat J, Garavan H, Heinz A, Ittermann B, Jia T, Lathrop M, Martinot JL, Nees F, Rietschel M, Smolka MN, Bartova L, Popovic A, Scharinger C, Sitte HH, Steiner H, Friedrich MH, Kasper S, Perkmann T, Praschak-Rieder N, Haslacher H, Esterbauer H, Moser E, Schumann G, Pezawas Let al., 2016, Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults, Brain Structure and Function, Vol: 221, Pages: 103-114, ISSN: 1863-2661

Prefrontal dopamine levels are relatively increased in adolescence compared to adulthood. Genetic variation of COMT (COMT Val158Met) results in lower enzymatic activity and higher dopamine availability in Met carriers. Given the dramatic changes of synaptic dopamine during adolescence, it has been suggested that effects of COMT Val158Met genotypes might have oppositional effects in adolescents and adults. The present study aims to identify such oppositional COMT Val158Met effects in adolescents and adults in prefrontal brain networks at rest. Resting state functional connectivity data were collected from cross-sectional and multicenter study sites involving 106 healthy young adults (mean age 24 ± 2.6 years), gender matched to 106 randomly chosen 14-year-olds. We selected the anterior medial prefrontal cortex (amPFC) as seed due to its important role as nexus of the executive control and default mode network. We observed a significant age-dependent reversal of COMT Val158Met effects on resting state functional connectivity between amPFC and ventrolateral as well as dorsolateral prefrontal cortex, and parahippocampal gyrus. Val homozygous adults exhibited increased and adolescents decreased connectivity compared to Met homozygotes for all reported regions. Network analyses underscored the importance of the parahippocampal gyrus as mediator of observed effects. Results of this study demonstrate that adolescent and adult resting state networks are dose-dependently and diametrically affected by COMT genotypes following a hypothetical model of dopamine function that follows an inverted U-shaped curve. This study might provide cues for the understanding of disease onset or dopaminergic treatment mechanisms in major neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder.

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Brossard M, Fang S, Vaysse A, Wei Q, Chen WV, Mohamdi H, Maubec E, Lavielle N, Galan P, Lathrop M, Avril M-F, Lee JE, Amos CI, Demenais Fet al., 2015, Integrated pathway and epistasis analysis reveals interactive effect of genetic variants at TERF1 and AFAP1L2 loci on melanoma risk, INTERNATIONAL JOURNAL OF CANCER, Vol: 137, Pages: 1901-1909, ISSN: 0020-7136

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• Citations: 8

Bouzigon E, Nadif R, Le Moual N, Dizier M-H, Aschard H, Boudier A, Bousquet J, Chanoine S, Donnay C, Dumas O, Gormand F, Jacquemin B, Just J, Margaritte-Jeannin P, Matran R, Pison C, Rage E, Rava M, Sarnowski C, Smit LAM, Temam S, Varraso R, Vignoud L, Lathrop M, Pin I, Demenais F, Kauffmann F, Siroux Vet al., 2015, Genetic and environmental factors of asthma and allergy: Results of the EGEA study, REVUE DES MALADIES RESPIRATOIRES, Vol: 32, Pages: 822-840, ISSN: 0761-8425

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• Citations: 12

Kiando SR, Barlassina C, Cusi D, Galan P, Lathrop M, Plouin P-F, Jeunemaitre X, Bouatia-Naji Net al., 2015, Exome sequencing in seven families and gene-based association studies indicate genetic heterogeneity and suggest possible candidates for fibromuscular dysplasia, JOURNAL OF HYPERTENSION, Vol: 33, Pages: 1802-1810, ISSN: 0263-6352

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• Citations: 23

Li Y, Cagirici HB, Horpaopan S, Ott J, Imai A, Majewski J, Lathrop Met al., 2015, Leveling the Playing Field in Homozygosity Mapping Using Map Distances, ANNALS OF HUMAN GENETICS, Vol: 79, Pages: 366-372, ISSN: 0003-4800

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• Citations: 1

Kinnersley B, Kamatani Y, Labussière M, Wang Y, Galan P, Mokhtari K, Delattre JY, Gousias K, Schramm J, Schoemaker MJ, Swerdlow A, Fleming SJ, Herms S, Heilmann S, Nöthen MM, Simon M, Sanson M, Lathrop M, Houlston RSet al., 2015, Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis, European Journal of Human Genetics, Vol: 24, Pages: 717-724, ISSN: 1476-5438

To identify protein-altering variants (PAVs) for glioma, we analysed Illumina HumanExome BeadChip exome-array data on 1882 glioma cases and 8079 controls from three independent European populations. In addition to single-variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally there was a strong relationship between effect size and PAVs predicted to be damaging (P=2.29 × 10(-49)); however, these variants which are most likely to impact on risk, are rare (MAF<5%). Although no single variant showed an association which was statistically significant at the genome-wide threshold a number represented promising associations - BRCA2:c.9976A>T, p.(Lys3326Ter), which has been shown to influence breast and lung cancer risk (odds ratio (OR)=2.3, P=4.00 × 10(-4) for glioblastoma (GBM)) and IDH2:c.782G>A, p.(Arg261His) (OR=3.21, P=7.67 × 10(-3), for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20 × 10(-6)). Genome scans of low-frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.

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Nicolas G, Wallon D, Charbonnier C, Quenez O, Rousseau S, Richard AC, Rovelet-Lecrux A, Coutant S, Le Guennec K, Bacq D, Garnier JG, Olaso R, Boland A, Meyer V, Deleuze JF, Munter HM, Bourque G, Auld D, Montpetit A, Lathrop M, Guyant-Maréchal L, Martinaud O, Pariente J, Rollin-Sillaire A, Pasquier F, Le Ber I, Sarazin M, Croisile B, Boutoleau-Bretonnière C, Thomas-Antérion C, Paquet C, Sauvée M, Moreaud O, Gabelle A, Sellal F, Ceccaldi M, Chamard L, Blanc F, Frebourg T, Campion D, Hannequin Det al., 2015, Screening of dementia genes by whole-exome sequencing in early-onset Alzheimer disease: input and lessons., European Journal of Human Genetics, Vol: 24, Pages: 710-716, ISSN: 1476-5438

Causative variants in APP, PSEN1 or PSEN2 account for a majority of cases of autosomal dominant early-onset Alzheimer disease (ADEOAD, onset before 65 years). Variant detection rates in other EOAD patients, that is, with family history of late-onset AD (LOAD) (and no incidence of EOAD) and sporadic cases might be much lower. We analyzed the genomes from 264 patients using whole-exome sequencing (WES) with high depth of coverage: 90 EOAD patients with family history of LOAD and no incidence of EOAD in the family and 174 patients with sporadic AD starting between 51 and 65 years. We found three PSEN1 and one PSEN2 causative, probably or possibly causative variants in four patients (1.5%). Given the absence of PSEN1, PSEN2 and APP causative variants, we investigated whether these 260 patients might be burdened with protein-modifying variants in 20 genes that were previously shown to cause other types of dementia when mutated. For this analysis, we included an additional set of 160 patients who were previously shown to be free of causative variants in PSEN1, PSEN2 and APP: 107 ADEOAD patients and 53 sporadic EOAD patients with an age of onset before 51 years. In these 420 patients, we detected no variant that might modify the function of the 20 dementia-causing genes. We conclude that EOAD patients with family history of LOAD and no incidence of EOAD in the family or patients with sporadic AD starting between 51 and 65 years have a low variant-detection rate in AD genes.

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Law MH, Bishop DT, Lee JE, Brossard M, Martin NG, Moses EK, Song F, Barrett JH, Kumar R, Easton DF, Pharoah PD, Swerdlow AJ, Kypreou KP, Taylor JC, Harland M, Randerson-Moor J, Akslen LA, Andresen PA, Avril MF, Azizi E, Scarrà GB, Brown KM, Dȩbniak T, Duffy DL, Elder DE, Fang S, Friedman E, Galan P, Ghiorzo P, Gillanders EM, Goldstein AM, Gruis NA, Hansson J, Helsing P, Hočevar M, Höiom V, Ingvar C, Kanetsky PA, Chen WV, GenoMEL Consortium, Essen-Heidelberg Investigators, SDH Study Group, Q-MEGA and QTWIN Investigators, AMFS Investigators, ATHENS Melanoma Study Group, Landi MT, Lang J, Lathrop GM, Lubiński J, Mackie RM, Mann GJ, Molven A, Montgomery GW, Novaković S, Olsson H, Puig S, Puig-Butille JA, Qureshi AA, Radford-Smith GL, van der Stoep N, van Doorn R, Whiteman DC, Craig JE, Schadendorf D, Simms LA, Burdon KP, Nyholt DR, Pooley KA, Orr N, Stratigos AJ, Cust AE, Ward SV, Hayward NK, Han J, Schulze HJ, Dunning AM, Bishop JA, Demenais F, Amos CI, MacGregor S, Iles MMet al., 2015, Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma, Nature Genetics, Vol: 47, Pages: 987-995, ISSN: 1546-1718

Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5 × 10(-8)), as did 2 previously reported but unreplicated loci and all 13 established loci. Newly associated SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes in the associated regions, including one involved in telomere biology.

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Lin X, Qi Q, Zheng Y, Huang T, Lathrop M, Zelenika D, Bray GA, Sacks FM, Liang L, Qi Let al., 2015, Neuropeptide Y genotype, central obesity, and abdominal fat distribution: the POUNDS LOST trial, AMERICAN JOURNAL OF CLINICAL NUTRITION, Vol: 102, Pages: 514-519, ISSN: 0002-9165

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• Citations: 21

Ojelade SA, Jia T, Rodan AR, Tao C, Kadrmas JL, Cattrell A, Ruggeri B, Charoen P, Lemaitre H, Banaschewski T, Buechel C, Bokde ALW, Carvalho F, Conrod PJ, Flor H, Frouin V, Gallinat J, Garavan H, Gowland PA, Heinz A, Ittermann B, Lathrop M, Lubbe S, Martinot J-L, Paus T, Smolka MN, Spanagel R, O'Reilly PF, Laitinen J, Veijola JM, Feng J, Desrivieres S, Jarvelin M-R, Schumann G, Rothenfluh Aet al., 2015, Rsu1 regulates ethanol consumption in Drosophila and humans, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 112, Pages: E4085-E4093, ISSN: 0027-8424

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• Citations: 40

Imai A, Nakaya A, Fahiminiya S, Tétreault M, Majewski J, Sakata Y, Takashima S, Lathrop M, Ott Jet al., 2015, Beyond homozygosity mapping: family-control analysis based on Hamming distance for prioritizing variants in exome sequencing, Scientific Reports, Vol: 5, ISSN: 2045-2322

A major challenge in current exome sequencing in autosomal recessive (AR) families is the lack of an effective method to prioritize single-nucleotide variants (SNVs). AR families are generally too small for linkage analysis, and length of homozygous regions is unreliable for identification of causative variants. Various common filtering steps usually result in a list of candidate variants that cannot be narrowed down further or ranked. To prioritize shortlisted SNVs we consider each homozygous candidate variant together with a set of SNVs flanking it. We compare the resulting array of genotypes between an affected family member and a number of control individuals and argue that, in a family, differences between family member and controls should be larger for a pathogenic variant and SNVs flanking it than for a random variant. We assess differences between arrays in two individuals by the Hamming distance and develop a suitable test statistic, which is expected to be large for a causative variant and flanking SNVs. We prioritize candidate variants based on this statistic and applied our approach to six patients with known pathogenic variants and found these to be in the top 2 to 10 percentiles of ranks.

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Kiando S, Plouin PF, Barlassina MC, Cusi D, Galan P, Lathrop M, Jeunemaitre X, Bouatia-Naji Net al., 2015, EXOME SEQUENCING IN SEVEN FAMILIES AND GENE-BASED ASSOCIATION STUDIES SUPPORT GENETIC HETEROGENEITY AND SUGGEST POSSIBLE CANDIDATES FOR FIBROMUSCULAR DYSPLASIA, JOURNAL OF HYPERTENSION, Vol: 33, Pages: E79-E79, ISSN: 0263-6352

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Das S, Stuart PE, Ding J, Tejasvi T, Li Y, Tsoi LC, Chandran V, Fischer J, Helms C, Duffin KC, Voorhees JJ, Bowcock AM, Krueger GG, Lathrop GM, Nair RP, Rahman P, Abecasis GR, Gladman D, Elder JTet al., 2015, Fine mapping of eight psoriasis susceptibility loci, EUROPEAN JOURNAL OF HUMAN GENETICS, Vol: 23, Pages: 844-853, ISSN: 1018-4813

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• Citations: 23

Allum F, Shao X, Guénard F, Simon MM, Busche S, Caron M, Lambourne J, Lessard J, Tandre K, Hedman Å, Kwan T, Ge B, Multiple Tissue Human Expression Resource Consortium, Rönnblom L, McCarthy MI, Deloukas P, Richmond T, Burgess D, Spector TD, Tchernof A, Marceau S, Lathrop M, Vohl MC, Pastinen T, Grundberg Eet al., 2015, Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants, Nature Communications, Vol: 6, ISSN: 2041-1723

Most genome-wide methylation studies (EWAS) of multifactorial disease traits use targeted arrays or enrichment methodologies preferentially covering CpG-dense regions, to characterize sufficiently large samples. To overcome this limitation, we present here a new customizable, cost-effective approach, methylC-capture sequencing (MCC-Seq), for sequencing functional methylomes, while simultaneously providing genetic variation information. To illustrate MCC-Seq, we use whole-genome bisulfite sequencing on adipose tissue (AT) samples and public databases to design AT-specific panels. We establish its efficiency for high-density interrogation of methylome variability by systematic comparisons with other approaches and demonstrate its applicability by identifying novel methylation variation within enhancers strongly correlated to plasma triglyceride and HDL-cholesterol, including at CD36. Our more comprehensive AT panel assesses tissue methylation and genotypes in parallel at ∼4 and ∼3 M sites, respectively. Our study demonstrates that MCC-Seq provides comparable accuracy to alternative approaches but enables more efficient cataloguing of functional and disease-relevant epigenetic and genetic variants for large-scale EWAS.

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Huang J, Chen J, Esparza J, Ding J, Elder JT, Abecasis GR, Lee Y-A, Lathrop GM, Moffatt MF, Cookson WOC, Liang Let al., 2015, eQTL mapping identifies insertion- and deletion-specific eQTLs in multiple tissues, NATURE COMMUNICATIONS, Vol: 6, ISSN: 2041-1723

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• Citations: 8

Chen D, Gaborieau V, Zhao Y, Chabrier A, Wang H, Waterboer T, Zaridze D, Lissowska J, Rudnai P, Fabianova E, Bencko V, Janout V, Foretova L, Mates IN, Szeszenia-Dabrowska N, Boffetta P, Pawlita M, Lathrop M, Gyllensten U, Brennan P, McKay JDet al., 2015, A systematic investigation of the contribution of genetic variation within the MHC region to HPV seropositivity, HUMAN MOLECULAR GENETICS, Vol: 24, Pages: 2681-2688, ISSN: 0964-6906

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• Citations: 8

Liang L, Willis-Owen SA, Laprise C, Wong KC, Davies GA, Hudson TJ, Binia A, Hopkin JM, Yang IV, Grundberg E, Busche S, Hudson M, Rönnblom L, Pastinen TM, Schwartz DA, Lathrop GM, Moffatt MF, Cookson WOet al., 2015, An epigenome-wide association study of total serum immunoglobulin E concentration, Nature, Vol: 520, Pages: 670-674, ISSN: 0028-0836

Immunoglobulin E (IgE) is a central mediator of allergic (atopic) inflammation. Therapies directed against IgE can alleviate hay fever and allergic asthma. Genetic association studies have not yet identified novel therapeutic targets or pathways underlying IgE regulation. We therefore surveyed epigenetic associations between serum IgE concentrations and methylation at loci concentrated in CpG islands genome wide in 95 nuclear pedigrees, using DNA from peripheral blood leukocytes. We validated positive results in additional families and in subjects from the general population. Here we show replicated associations-with a meta-analysis false discovery rate less than 10(-4)-between IgE and low methylation at 36 loci. Genes annotated to these loci encode known eosinophil products, and also implicate phospholipid inflammatory mediators, specific transcription factors and mitochondrial proteins. We confirmed that methylation at these loci differed significantly in isolated eosinophils from subjects with and without asthma and high IgE levels. The top three loci accounted for 13% of IgE variation in the primary subject panel, explaining the tenfold higher variance found compared with that derived from large single-nucleotide polymorphism genome-wide association studies. This study identifies novel therapeutic targets and biomarkers for patient stratification for allergic diseases.

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Bouzigon E, Nadif R, Thompson EE, Concas MP, Kuldanek S, Du G, Brossard M, Lavielle N, Sarnowski C, Vaysse A, Dessen P, van der Valk RJP, Duijts L, Henderson AJ, Jaddoe VWV, de Jongste JC, Casula S, Biino G, Dizier M-H, Pin I, Matran R, Lathrop M, Pirastu M, Demenais F, Ober Cet al., 2015, A common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 45, Pages: 797-806, ISSN: 0954-7894

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• Citations: 8

Henrion MY, Purdue MP, Scelo G, Broderick P, Frampton M, Ritchie A, Meade A, Li P, McKay J, Johansson M, Lathrop M, Larkin J, Rothman N, Wang Z, Chow WH, Stevens VL, Diver WR, Albanes D, Virtamo J, Brennan P, Eisen T, Chanock S, Houlston RSet al., 2015, Common Variation at 1q24.1 (ALDH9A1) Is a Potential Risk Factor for Renal Cancer, PLOS One, Vol: 10, ISSN: 1932-6203

So far six susceptibility loci for renal cell carcinoma (RCC) have been discovered by genome-wide association studies (GWAS). To identify additional RCC common risk loci, we performed a meta-analysis of published GWAS (totalling 2,215 cases and 8,566 controls of Western-European background) with imputation using 1000 Genomes Project and UK10K Project data as reference panels and followed up the most significant association signals [22 single nucleotide polymorphisms (SNPs) and 3 indels in eight genomic regions] in 383 cases and 2,189 controls from The Cancer Genome Atlas (TCGA). A combined analysis identified a promising susceptibility locus mapping to 1q24.1 marked by the imputed SNP rs3845536 (Pcombined =2.30x10-8). Specifically, the signal maps to intron 4 of the ALDH9A1 gene (aldehyde dehydrogenase 9 family, member A1). We further evaluated this potential signal in 2,461 cases and 5,081 controls from the International Agency for Research on Cancer (IARC) GWAS of RCC cases and controls from multiple European regions. In contrast to earlier findings no association was shown in the IARC series (P=0.94; Pcombined =2.73x10-5). While variation at 1q24.1 represents a potential risk locus for RCC, future replication analyses are required to substantiate our observation.

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Barrett JH, Taylor JC, Bright C, Harland M, Dunning AM, Akslen LA, Andresen PA, Avril M-F, Azizi E, Scarra GB, Brossard M, Brown KM, Debniak T, Elder DE, Friedman E, Ghiorzo P, Gillanders EM, Gruis NA, Hansson J, Helsing P, Hocevar M, Hoiom V, Ingvar C, Landi MT, Lang J, Lathrop GM, Lubinski J, Mackie RM, Molven A, Novakovic S, Olsson H, Puig S, Anton Puig-Butille J, van der Stoep N, van Doorn R, van Workum W, Goldstein AM, Kanetsky PA, Pharoah PDP, Demenais F, Hayward NK, Newton Bishop JA, Bishop DT, Iles MMet al., 2015, Fine mapping of genetic susceptibility loci for melanoma reveals a mixture of single variant and multiple variant regions, INTERNATIONAL JOURNAL OF CANCER, Vol: 136, Pages: 1351-1360, ISSN: 0020-7136

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• Citations: 19

O'Dushlaine C, Rossin L, Lee PH, Duncan L, Parikshak NN, Newhouse S, Ripke S, Neale BM, Purcell SM, Posthuma D, Nurnberger JI, Lee SH, Faraone SV, Perlis RH, Mowry BJ, Thapar A, Goddard ME, Witte JS, Absher D, Agartz I, Akil H, Amin F, Andreassen OA, Anjorin A, Anney R, Anttila V, Arking DE, Asherson P, Azevedo MH, Backlund L, Badner JA, Bailey AJ, Banaschewski T, Barchas JD, Barnes MR, Barrett TB, Bass N, Battaglia A, Bauer M, Bayes M, Bellivier F, Bergen SE, Berrettini W, Betancur C, Bettecken T, Biederman J, Binder EB, Black DW, Blackwood DHR, Bloss CS, Boehnke M, Boomsma DI, Breuer R, Bruggeman R, Cormican P, Buccola NG, Buitelaar JK, Bunney WE, Buxbaum JD, Byerley WF, Byrne EM, Caesar S, Cahn W, Cantor RM, Casas M, Chakravarti A, Chambert K, Choudhury K, Cichon S, Mattheisen M, Cloninger CR, Collier DA, Cook EH, Coon H, Cormand B, Corvin A, Coryell WH, Craig DW, Craig IW, Crosbie J, Cuccaro ML, Curtis D, Czamara D, Datta S, Dawson G, Day R, De Geus EJ, Degenhardt F, Djurovic S, Donohoe GJ, Doyle AE, Duan J, Dudbridge F, Duketis E, Ebstein RP, Edenberg HJ, Elia J, Ennis S, Etain B, Fanous A, Farmer AE, Ferrier IN, Flicldnger M, Fombonne E, Foroud T, Frank J, Franke B, Fraser C, Freedman R, Freimer NB, Freitag CM, Friedl M, Frisen L, Gailagher L, Gejman PV, Georgieva L, Gershon ES, Giegling I, Gill M, Gordon SD, Gordon-Smith K, Green EK, Greenwood TA, Grice DE, Gross M, Grozeva D, Guan W, Gurling H, De Haan L, Haines JL, Hakonarson H, Hallmayer J, Hamilton SP, Hamshere ML, Hansen TF, Hartmann AM, Hautzinger M, Heath AC, Henders AK, Herms S, Hickie IB, Hipolito M, Hoefels S, Holsboer F, Hoogendijk WJ, Hottenga J-J, Hultman CM, Hus V, Ingason A, Ising M, Jamain S, Jones EG, Jones I, Jones L, Tzeng J-Y, Kaehler AK, Kahn RS, Kandaswamy R, Keller MC, Kennedy JL, Kenny E, Kent L, Kim Y, Kirov GK, Klauck SM, Klei L, Knowles JA, Kohli MA, Koller DL, Konte B, Korszun A, Krabbendam L, Krasucki R, Kuntsi J, Kwan P, Landen M, Laengstroem N, Lathrop M, Lawrence J, Lawson WBet al., 2015, Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways, NATURE NEUROSCIENCE, Vol: 18, Pages: 199-209, ISSN: 1097-6256

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• Citations: 447

Desrivieres S, Lourdusamy A, Tao C, Toro R, Jia T, Loth E, Medina LM, Kepa A, Fernandes A, Ruggeri B, Carvalho FM, Cocks G, Banaschewski T, Barker GJ, Bokde ALW, Buechel C, Conrod PJ, Flor H, Heinz A, Gallinat J, Garavan H, Gowland P, Bruehl R, Lawrence C, Mann K, Martinot MLP, Nees F, Lathrop M, Poline J-B, Rietschel M, Thompson P, Fauth-Buehler M, Smolka MN, Pausova Z, Paus T, Feng J, Schumann Get al., 2015, Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents, MOLECULAR PSYCHIATRY, Vol: 20, Pages: 263-274, ISSN: 1359-4184

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• Citations: 31

Torre S, Faucher SP, Fodil N, Bongfen SE, Berghout J, Schwartzentruber JA, Majewski J, Lathrop M, Cooper AM, Vidal SM, Gros Pet al., 2015, THEMIS Is Required for Pathogenesis of Cerebral Malaria and Protection against Pulmonary Tuberculosis, INFECTION AND IMMUNITY, Vol: 83, Pages: 759-768, ISSN: 0019-9567

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• Citations: 12

Debette S, Kamatani Y, Metso TM, Kloss M, Chauhan G, Engelter ST, Pezzini A, Thijs V, Markus HS, Dichgans M, Wolf C, Dittrich R, Touze E, Southerland AM, Samson Y, Abboud S, Bejot Y, Caso V, Bersano A, Gschwendtner A, Sessa M, Cole J, Lamy C, Medeiros E, Beretta S, Bonati LH, Grau AJ, Michel P, Majersik JJ, Sharma P, Kalashnikova L, Nazarova M, Dobrynina L, Bartels E, Guillon B, van den Herik EG, Fernandez-Cadenas I, Jood K, Nalls MA, De Leeuw F-E, Jern C, Cheng Y-C, Werner I, Metso AJ, Lichy C, Lyrer PA, Brandt T, Boncoraglio GB, Wichmann H-E, Gieger C, Johnson AD, Bottcher T, Castellano M, Arveiler D, Ikram MA, Breteler MMB, Padovani A, Meschia JF, Kuhlenbaumer G, Rolfs A, Worrall BB, Ringelstein E-B, Zelenika D, Tatlisumak T, Lathrop M, Leys D, Amouyel P, Dallongeville J, Lemmens R, Pandolfo M, Bodenant M, Louillet F, Mas JL, Deltour S, Leder S, Leger A, Canaple S, Godefroy O, Giroud M, Jacquin A, Moulin T, Vullier F, Tzourio C, Dos Santos M, Malik R, Hausser I, Thomas-Feles C, Weber R, Grond-Ginsbach C, Hacke W, Giossi A, Volonghi I, Costa P, del Zotto E, Morotti A, Poli L, Muiesan ML, Salvetti M, Rosei EA, Lanfranconi S, Baron P, Ferrarese C, Susani E, Bicocca M, Giacalone G, Paolucci S, Palmirotta R, Guadagni F, Paciaroni M, Ballabio E, Parati EA, Ciusani E, Fluri F, Hatz F, Gisler D, Amort M, Bevan S, James T, Olsson S, Holmegaard L, Altintas A, Martin JJ, Kittner S, MItchell B, Stine C, O'Connell J, Dueker N, Koudstaal PJ, de Lau LM, Hofman A, Verhaaren BF, Uitterlinden AG, Montaner J, Mendioroz M, Yadav S, Khan MS, Wilder M, van Dijk E, Maaijwee N, Rutten-Jacobs L, Kramer J, Malik S, Brown RD, Singleton A, Hardy J, Rich SS, Tanislav C, Jungehuelsing Jet al., 2015, Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection, NATURE GENETICS, Vol: 47, Pages: 78-+, ISSN: 1061-4036

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• Citations: 113

Wang Z, Zhu B, Zhang M, Parikh H, Jia J, Chung CC, Sampson JN, Hoskins JW, Hutchinson A, Burdette L, Ibrahim A, Hautman C, Raj PS, Abnet CC, Adjei AA, Ahlbom A, Albanes D, Allen NE, Ambrosone CB, Aldrich M, Amiano P, Amos C, Andersson U, Andriole G, Andrulis IL, Arici C, Arslan AA, Austin MA, Baris D, Barkauskas DA, Bassig BA, Freeman LEB, Berg CD, Berndt SI, Bertazzi PA, Biritwum RB, Black A, Blot W, Boeing H, Boffetta P, Bolton K, Boutron-Ruault M-C, Bracci PM, Brennan P, Brinton LA, Brotzman M, Bueno-de-Mesquita HB, Buring JE, Butler MA, Cai Q, Cancel-Tassin G, Canzian F, Cao G, Caporaso NE, Carrato A, Carreon T, Carta A, Chang G-C, Chang I-S, Chang-Claude J, Che X, Chen C-J, Chen C-Y, Chen C-H, Chen C, Chen K-Y, Chen Y-M, Chokkalingam AP, Chu LW, Clavel-Chapelon F, Colditz GA, Colt JS, Conti D, Cook MB, Cortessis VK, Crawford ED, Cussenot O, Davis FG, De Vivo I, Deng X, Ding T, Dinney CP, Di Stefano AL, Diver WR, Duell EJ, Elena JW, Fan J-H, Feigelson HS, Feychting M, Figueroa JD, Flanagan AM, Fraumeni JF, Freedman ND, Fridley BL, Fuchs CS, Gago-Dominguez M, Gallinger S, Gao Y-T, Gapstur SM, Garcia-Closas M, Garcia-Closas R, Gastier-Foster JM, Gaziano JM, Gerhard DS, Giffen CA, Giles GG, Gillanders EM, Giovannucci EL, Goggins M, Gokgoz N, Goldstein AM, Gonzalez C, Gorlick R, Greene MH, Gross M, Grossman HB, Grubb R, Gu J, Guan P, Haiman CA, Hallmans G, Hankinson SE, Harris CC, Hartge P, Hattinger C, Hayes RB, He Q, Helman L, Henderson BE, Henriksson R, Hoffman-Bolton J, Hohensee C, Holly EA, Hong Y-C, Hoover RN, Hosgood HD, Hsiao C-F, Hsing AW, Hsiung CA, Hu N, Hu W, Hu Z, Huang M-S, Hunter DJ, Inskip PD, Ito H, Jacobs EJ, Jacobs KB, Jenab M, Ji B-T, Johansen C, Johansson M, Johnson A, Kaaks R, Kamat AM, Kamineni A, Karagas M, Khanna C, Khaw K-T, Kim C, Kim I-S, Kim JH, Kim YH, Kim Y-C, Kim YT, Kang CH, Jung YJ, Kitahara CM, Klein AP, Klein R, Kogevinas M, Koh W-P, Kohno T, Kolonel LN, Kooperberg C, Kratz CP, Krogh V, Kunitoh H, Kurtz RC, Kurucu N, Lan Q, Lathroet al., 2014, Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33, HUMAN MOLECULAR GENETICS, Vol: 23, Pages: 6616-6633, ISSN: 0964-6906

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• Citations: 68

Gilbert R, Bonilla C, Metcalfe C, Lewis S, Evans DM, Fraser WD, Kemp JP, Donovan JL, Hamdy FC, Neal DE, Lane JA, Smith GD, Lathrop M, Martin RMet al., 2014, Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer: a nested case-control study, Cancer Causes & Control, Vol: 26, Pages: 205-218, ISSN: 1573-7225

PURPOSE: Vitamin D pathway single nucleotide polymorphisms (SNPs) are potentially useful proxies for investigating whether circulating vitamin D metabolites [total 25-hydroxyvitamin-D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)2D] are causally related to prostate cancer. We investigated associations of sixteen SNPs across seven genes with prostate-specific antigen-detected prostate cancer. METHODS: In a nested case-control study (within the ProtecT trial), we estimated odds ratios and 95 % confidence intervals (CIs) quantifying associations between SNPs and prostate cancer. Subgroup analyses investigated whether associations were stronger in men who had high/low sun exposure [a proxy for 25(OH)D]. We quantified associations of SNPs with stage (T1-T2/T3-T4) and grade (<7/≥7). Multiple variant scores included SNPs encoding proteins involved in 25(OH)D synthesis and metabolism. RESULTS: We included 1,275 prostate cancer cases (141 locally advanced, 385 high grades) and 2,062 healthy controls. Vitamin D-binding protein SNPs were associated with prostate cancer (rs4588-A: OR 1.20, CI 1.01, 1.41, p = 0.04; rs7041-T: OR 1.19, CI 1.02, 1.38, p = 0.03). Low 25(OH)D metabolism score was associated with high (vs low) grade (OR 0.76, CI 0.63, 0.93, p = 0.01); there was a similar association of its component variants: rs6013897-A in CYP24A1 (OR 0.78, CI 0.60, 1.01, p = 0.06) and rs10877012-T in CYP27B1 (OR 0.80, CI 0.63, 1.02, p = 0.07). There was no evidence that associations differed by level of sun exposure. CONCLUSION: We found some evidence that vitamin D pathway SNPs were associated with prostate cancer risk and grade, but not stage. There was no evidence of an association in men with deficient vitamin D (measured by having low sun exposure).

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Chouraki V, De Bruijn RFAG, Chapuis J, Bis JC, Reitz C, Schraen S, Ibrahim-Verbaas CA, Grenier-Boley B, Delay C, Rogers R, Demiautte F, Mounier A, Fitzpatrick AL, Berr C, Dartigues J-F, Uitterlinden AG, Hofman A, Breteler M, Becker JT, Lathrop M, Schupf N, Alperovitch A, Mayeux R, van Duijn CM, Buee L, Amouyel P, Lopez OL, Ikram MA, Tzourio C, Lambert J-Cet al., 2014, A genome-wide association meta-analysis of plasma A beta peptides concentrations in the elderly, MOLECULAR PSYCHIATRY, Vol: 19, Pages: 1326-1335, ISSN: 1359-4184

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• Citations: 23

Kennedy JM, Fodil N, Torre S, Bongfen SE, Olivier J-F, Leung V, Langlais D, Meunier C, Berghout J, Langat P, Schwartzentruber J, Majewski J, Lathrop M, Vidal SM, Gros Pet al., 2014, CCDC88B is a novel regulator of maturation and effector functions of T cells during pathological inflammation, Journal of Experimental Medicine, Vol: 211, Pages: 2519-2535, ISSN: 0022-1007

We used a genome-wide screen in mutagenized mice to identify genes which inactivation protects against lethal neuroinflammation during experimental cerebral malaria (ECM). We identified an ECM-protective mutation in coiled-coil domain containing protein 88b (Ccdc88b), a poorly annotated gene that is found expressed specifically in spleen, bone marrow, lymph nodes, and thymus. The CCDC88B protein is abundantly expressed in immune cells, including both CD4+ and CD8+ T lymphocytes, and in myeloid cells, and loss of CCDC88B protein expression has pleiotropic effects on T lymphocyte functions, including impaired maturation in vivo, significantly reduced activation, reduced cell division as well as impaired cytokine production (IFN- and TNF) in response to T cell receptor engage-ment, or to nonspecific stimuli in vitro, and during the course of P. berghei infection in vivo. This identifies CCDC88B as a novel and important regulator of T cell function. The human CCDC88B gene maps to the 11q13 locus that is associated with susceptibility to several inflammatory and auto-immune disorders. Our findings strongly suggest that CCDC88B is the morbid gene underlying the pleiotropic effect of the 11q13 locus on inflammation.

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Ratnapriya R, Zhan X, Fariss RN, Branham KE, Zipprer D, Chakarova CF, Sergeev YV, Campos MM, Othman M, Friedman JS, Maminishkis A, Waseem NH, Brooks M, Rajasimha HK, Edwards AO, Lotery A, Klein BE, Truitt BJ, Li B, Schaumberg DA, Morgan DJ, Morrison MA, Souied E, Tsironi EE, Grassmann F, Fishman GA, Silvestri G, Scholl HPN, Kim IK, Ramke J, Tuo J, Merriam JE, Merriam JC, Park KH, Olson LM, Farrer LA, Johnson MP, Peachey NS, Lathrop M, Baron RV, Igo RP, Klein R, Hagstrom SA, Kamatani Y, Martin TM, Jiang Y, Conley Y, Sahel J-A, Zack DJ, Chan C-C, Pericak-Vance MA, Jacobson SG, Gorin MB, Klein ML, Allikmets R, Iyengar SK, Weber BH, Haines JL, Leveillard T, Deangelis MM, Stambolian D, Weeks DE, Bhattacharya SS, Chew EY, Heckenlively JR, Abecasis GR, Swaroop Aet al., 2014, Rare and common variants in extracellular matrix gene Fibrillin 2 (FBN2) are associated with macular degeneration, HUMAN MOLECULAR GENETICS, Vol: 23, Pages: 5827-5837, ISSN: 0964-6906

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• Citations: 33