Sosina W Tilahun, Leul D Kitaw, Nete T Yusuf
Predictors of information needs among women with breast cancer receiving adjuvant therapy at Tikur Anbessa specialized hospital, Addis Ababa Ethiopia: a cross-sectional study
BMC women's health
additional genetic variants circulating antimllerian hormone amh levels identified genomewide association study gwas metaanalysis including large sample premenopausal women identified four loci associated amh levels p 5 108 previously reported mcm8 locus three novel signals near amh tex41 cdca7 amh expressed antral stage ovarian follicles women variation agespecific circulating amh levels associated disease outcomes however physiological mechanisms underlying amhdisease associations largely unknown performed gwas metaanalysis combined summary statistics previous amh gwas gwas data 3705 additional women three different cohorts total included data 7049 premenopausal female participants european ancestry median age study participants ranged 153 48 years across cohorts circulating amh levels measured either serum plasma samples using different elisa assays studyspecific analyses adjusted age blood collection population stratification summary statistics metaanalysed using standard errorweighted approach subsequently functionally annotated gwas variants reached genomewide significance p 5 108 also performed genebased gwas pathway analysis linkage disequilibrium score regression mendelian randomization mr analyses identified four loci associated amh levels p 5 108 previously reported mcm8 locus three novel signals near amh tex41 cdca7 strongest signal missense variant amh gene rs10417628 prioritized genes three identified loci involved cell cycle regulation genetic correlation analyses indicated strong positive correlation among single nucleotide polymorphisms amh levels age menopause rg 082 fdr 0003 exploratory twosample mr analyses support causal effects amh breast cancer polycystic ovary syndrome risk interpreted caution may underpowered validity genetic instruments could extensively explored full amh gwas summary statistics made available publication gwas catalog httpswwwebiacukgwas whilst study doubled sample size recent gwas statistical power still relatively low result may still lack power identify genetic variants amh determine causal effects amh example breast cancer also followup studies needed investigate whether signal amh gene caused reduced amh detection certain assays instead actual lower circulating amh levels genes mapped mcm8 tex41 cdca7 loci involved cell cycle processes dna replication apoptosis mechanism underlying associations amh may affect size ovarian follicle pool altogether results provide insight biology amh accordingly biological processes involved ovarian ageing nurses health study nurses health study ii supported research grants national institutes health ca172726 ca186107 ca50385 ca87969 ca49449 ca67262 ca178949 uk medical research council wellcome 217065z19z university bristol provide core support alspac publication work listed authors serve guarantors contents article comprehensive list grants funding available alspac website httpwwwbristolacukalspacexternaldocumentsgrantacknowledgementspdf funding collection genotype phenotype data used provided british heart foundation sp0700824066 wellcome wt092830m wt08806 uk medical research council g1001357 mcb algs dal work unit funded university bristol uk medical research council mcuu000116 mcbs contribution work funded uk medical research council skills development fellowship mrp0140541 dal national institute health research senior investigator nf061610102 algs supported study dynamic longitudinal exposome trajectories cardiovascular metabolic noncommunicable diseases h2020sc12019singlestagertd project id 874739 doetinchem cohort study financially supported ministry health welfare sports netherlands funder role study design data collection analysis decision publish preparation manuscript ansh labs performed amh measurements doetinchem cohort study free charge ansh labs involved data analysis interpretation reporting financially involved aspect study rmgv funded honours track msc epidemiology university medical center utrecht grant netherlands organization scientific research nwo 022005021 study womens health across nation swan grant support national institutes health nih dhhs national institute aging nia national institute nursing research ninr nih office research womens health orwh u01nr004061 u01ag012505 u01ag012535 u01ag012531 u01ag012539 u01ag012546 u01ag012553 u01ag012554 u01ag012495 swan genomic analyses swan legacy grant support nia u01ag017719 generations study funded breast cancer institute cancer research icr icr acknowledges nhs funding nihr biomedical research centre content manuscript solely responsibility authors necessarily represent official views funders sister study funded intramural research program national institutes health nih national institute environmental health sciences z01es044005 dps amh assays supported avon foundation 022012065 hb nichols dps breast cancer genomewide association analyses supported government canada genome canada canadian institutes health research ministre de lconomie de la science et de linnovation du qubec genome qubec grant psrsiiri701 national institutes health u19 ca148065 x01hg007492 cancer research uk c1287a10118 c1287a16563 c1287a10710 european union healthf22009223175 h2020 633784 634935 studies funders listed michailidou et al nature 2017 fjmb received fees grant support merck serono ferring bv dal received financial support several national international government charitable funders well medtronic ltd roche diagnostics research unrelated study ns scientific consultant ansh laboratories authors declare competing interests