WHOLE GENOME SEQUENCING ANALYSIS OF BODY MASS INDEX IDENTIFIES NOVEL AFRICAN ANCESTRY-SPECIFIC RISK ALLELE.
Xinruo ZhangJennifer A BrodyMariaelisa GraffHeather M HighlandNathalie ChamiHanfei XuZhe WangKendra FerrierGeetha ChittoorNavya S JosyulaXihao LiZilin LiMatthew A AllisonDiane M BeckerLawrence F BielakJoshua C BisMeher Preethi BoorgulaDonald W BowdenJai G BroomeErin J ButhChristopher S CarlsonKyong-Mi ChangSameer ChavanYen-Feng ChiuLee-Ming ChuangMatthew P ConomosDawn L DeMeoMargaret DuRavindranath DuggiralaCeleste EngAlison E FohnerBarry I FreedmanMelanie E GarrettXiuqing GuoChristopher A HaimanBenjamin D HeavnerBertha A HidalgoJames E HixsonYuk-Lam Anne HoBrian D HobbsDonglei HuQin HuiChii-Min HwuRebecca D JacksonDeepti JainRita R KalyaniSharon L R KardiaTanika N KellyEthan M LangeMichael LeNoirChangwei LiLoic Le MarchandMerry-Lynn N McDonaldCaitlin P McHughAlanna C MorrisonTake Naserinull nullJeffrey O'ConnellChristopher J O'DonnellNicholette D D AllredJames S PankowJames A PerryUlrike PetersMichael H PreussD C RaoElizabeth A ReganSefuiva M ReupenaDan M RodenJose Rodriguez-SantanaColleen M SitlaniJennifer A SmithHemant K TiwariRamachandran S VasanZeyuan WangDaniel E WeeksJennifer WesselKerri L WigginsLynne R WilkensPeter W F WilsonLisa R YanekZachary T YonedaWei ZhaoSebastian ZöllnerDonna K ArnettAllison Elizabeth Ashley-KochKathleen C BarnesJohn E BlangeroEric BoerwinkleEsteban G BurchardApril P CarsonDaniel I ChasmanYii-Der Ida ChenJoanne E CurranMyriam FornageVictor R GordeukJiang HeSusan R HeckbertLifang HouMarguerite R IrvinCharles KooperbergRyan L MinsterBraxton D MitchellSeyed Mehdi NouraieBruce M PsatyLaura M RaffieldAlexander P ReinerStephen S RichJerome I RotterM Benjamin ShoemakerNicholas L SmithKent D TaylorMarilyn J TelenScott T WeissYingze ZhangNancy Heard- CostaYan V SunXihong LinL Adrienne CupplesLeslie A LangeChing-Ti LiuRuth J F LoosKari E NorthAnne E JusticePublished in: medRxiv : the preprint server for health sciences (2023)
Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups. We discovered 18 BMI-associated signals ( P < 5 × 10 -9 ). Notably, we identified and replicated a novel low frequency single nucleotide polymorphism (SNP) in MTMR3 that was common in individuals of African descent. Using a diverse study population, we further identified two novel secondary signals in known BMI loci and pinpointed two likely causal variants in the POC5 and DMD loci. Our work demonstrates the benefits of combining WGS and diverse cohorts in expanding current catalog of variants and genes confer risk for obesity, bringing us one step closer to personalized medicine.
Keyphrases
- body mass index
- weight gain
- genome wide
- public health
- genome wide association
- insulin resistance
- metabolic syndrome
- copy number
- type diabetes
- weight loss
- physical activity
- high fat diet induced
- quality improvement
- cardiovascular disease
- adipose tissue
- risk factors
- duchenne muscular dystrophy
- transcription factor
- genome wide identification